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Inhibition of Mammalian target of rapamycin in human acute myeloid leukemia cells has diverse effects that depend on the environmental in vitro stress. 抑制雷帕霉素哺乳动物靶标在人类急性髓性白血病细胞中的作用多种多样,取决于体外环境压力。
Bone Marrow Research Pub Date : 2012-01-01 Epub Date: 2012-10-02 DOI: 10.1155/2012/329061
Anita Ryningen, Håkon Reikvam, Ina Nepstad, Kristin Paulsen Rye, Oystein Bruserud
{"title":"Inhibition of Mammalian target of rapamycin in human acute myeloid leukemia cells has diverse effects that depend on the environmental in vitro stress.","authors":"Anita Ryningen, Håkon Reikvam, Ina Nepstad, Kristin Paulsen Rye, Oystein Bruserud","doi":"10.1155/2012/329061","DOIUrl":"10.1155/2012/329061","url":null,"abstract":"<p><p>Effects of the mTOR inhibitor rapamycin were characterized on in vitro cultured primary human acute myeloid leukemia (AML) cells and five AML cell lines. Constitutive mTOR activation seemed to be a general characteristic of primary AML cells. Increased cellular stress induced by serum deprivation increased both mTOR signaling, lysosomal acidity, and in vitro apoptosis, where lysosomal acidity/apoptosis were independent of increased mTOR signaling. Rapamycin had antiproliferative and proapoptotic effects only for a subset of patients. Proapoptotic effect was detected for AML cell lines only in the presence of serum. Combination of rapamycin with valproic acid, all-trans retinoic acid (ATRA), and NF-κB inhibitors showed no interference with constitutive mTOR activation and mTOR inhibitory effect of rapamycin and no additional proapoptotic effect compared to rapamycin alone. In contrast, dual inhibition of the PI3K-Akt-mTOR pathway by rapamycin plus a PI3K inhibitor induced new functional effects that did not simply reflect a summary of single drug effects. To conclude, (i) pharmacological characterization of PI3K-Akt-mTOR inhibitors requires carefully standardized experimental models, (ii) rapamycin effects differ between patients, and (iii) combined targeting of different steps in this pathway should be further investigated whereas combination of rapamycin with valproic acid, ATRA, or NF-κB inhibitors seems less promising.</p>","PeriodicalId":9220,"journal":{"name":"Bone Marrow Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3467767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30987210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Autologous stem cell transplant for Al amyloidosis. 自体干细胞移植治疗阿尔淀粉样变性病。
Bone Marrow Research Pub Date : 2012-01-01 Epub Date: 2012-05-16 DOI: 10.1155/2012/238961
Vivek Roy
{"title":"Autologous stem cell transplant for Al amyloidosis.","authors":"Vivek Roy","doi":"10.1155/2012/238961","DOIUrl":"10.1155/2012/238961","url":null,"abstract":"<p><p>AL amyloidosis is caused by clonal plasma cells that produce immunoglobulin light chains which misfold and get deposited as amyloid fibrils. Therapy directed against the plasma cell clone leads to clinical benefit. Melphalan and corticosteroids have been the mainstay of treatment for a number of years and the recent availability of other effective agents (IMiDs and proteasome inhibitors) has increased treatment options. Autologous stem cell transplant (ASCT) has been used in the treatment of AL amyloidosis for many years. It is associated with high rates of hematologic response and improvement in organ function. However, transplant carries considerable risks. Careful patient selection is important to minimize transplant related morbidity and mortality and ensure optimal patient outcomes. As newer more affective therapies become available the role and timing of ASCT in the overall treatment strategy of AL amyloidosis will need to be continually reassessed.</p>","PeriodicalId":9220,"journal":{"name":"Bone Marrow Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3361989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30672933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Curability of multiple myeloma. 多发性骨髓瘤的治愈率。
Bone Marrow Research Pub Date : 2012-01-01 Epub Date: 2012-05-23 DOI: 10.1155/2012/916479
Raymond Alexanian, Kay Delasalle, Michael Wang, Sheeba Thomas, Donna Weber
{"title":"Curability of multiple myeloma.","authors":"Raymond Alexanian,&nbsp;Kay Delasalle,&nbsp;Michael Wang,&nbsp;Sheeba Thomas,&nbsp;Donna Weber","doi":"10.1155/2012/916479","DOIUrl":"https://doi.org/10.1155/2012/916479","url":null,"abstract":"<p><p>Among 792 patients with multiple myeloma treated from 1987 to 2010 and assessed after 18 months, there were 167 patients with complete remission. For those 60 patients treated between 1987-1998 and with long followup, the latest relapse occurred after 11.8 years, so that 13 patients have remained in sustained complete remission for longer than 12 years (range 12-22 years). These results suggest that 3% of all patients treated during that period may be cured of multiple myeloma. In addition to immunofixation, more sensitive techniques for the detection of residual disease should be applied more consistently in patients with apparent complete remission in order to identify those with potential cure.</p>","PeriodicalId":9220,"journal":{"name":"Bone Marrow Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/916479","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30672934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 25
Unrelated hematopoietic stem cell donor matching probability and search algorithm. 非亲属造血干细胞供体匹配概率及搜索算法。
Bone Marrow Research Pub Date : 2012-01-01 Epub Date: 2012-11-13 DOI: 10.1155/2012/695018
J-M Tiercy
{"title":"Unrelated hematopoietic stem cell donor matching probability and search algorithm.","authors":"J-M Tiercy","doi":"10.1155/2012/695018","DOIUrl":"https://doi.org/10.1155/2012/695018","url":null,"abstract":"<p><p>In transplantation of hematopoietic stem cells (HSCs) from unrelated donors a high HLA compatibility level decreases the risk of acute graft-versus-host disease and mortality. The diversity of the HLA system at the allelic and haplotypic level and the heterogeneity of HLA typing data of the registered donors render the search process a complex task. This paper summarizes our experience with a search algorithm that includes at the start of the search a probability estimate (high/intermediate/low) to identify a HLA-A, B, C, DRB1, DQB1-compatible donor (a 10/10 match). Based on 2002-2011 searches about 30% of patients have a high, 30% an intermediate, and 40% a low probability search. Search success rate and duration are presented and discussed in light of the experience of other centers. Overall a 9-10/10 matched HSC donor can now be identified for 60-80% of patients of European descent. For high probability searches donors can be selected on the basis of DPB1-matching with an estimated success rate of >40%. For low probability searches there is no consensus on which HLA incompatibilities are more permissive, although HLA-DQB1 mismatches are generally considered as acceptable. Models for the discrimination of more detrimental mismatches based on specific amino acid residues rather than specific HLA alleles are presented.</p>","PeriodicalId":9220,"journal":{"name":"Bone Marrow Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/695018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31088069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 35
Human leukocyte antigen profiles of latin american populations: differential admixture and its potential impact on hematopoietic stem cell transplantation. 拉丁美洲人群的人类白细胞抗原谱:差异混合物及其对造血干细胞移植的潜在影响。
Bone Marrow Research Pub Date : 2012-01-01 Epub Date: 2012-11-18 DOI: 10.1155/2012/136087
Esteban Arrieta-Bolaños, J Alejandro Madrigal, Bronwen E Shaw
{"title":"Human leukocyte antigen profiles of latin american populations: differential admixture and its potential impact on hematopoietic stem cell transplantation.","authors":"Esteban Arrieta-Bolaños,&nbsp;J Alejandro Madrigal,&nbsp;Bronwen E Shaw","doi":"10.1155/2012/136087","DOIUrl":"https://doi.org/10.1155/2012/136087","url":null,"abstract":"<p><p>The outcome of hematopoietic stem cell transplantation (HSCT) is shaped by both clinical and genetic factors that determine its success. Genetic factors including human leukocyte antigen (HLA) and non-HLA genetic variants are believed to influence the risk of potentially fatal complications after the transplant. Moreover, ethnicity has been proposed as a factor modifying the risk of graft-versus-host disease. The populations of Latin America are a complex array of different admixture processes with varying degrees of ancestral population proportions that came in different migration waves. This complexity makes the study of genetic risks in this region complicated unless the extent of this variation is thoroughly characterized. In this study we compared the HLA-A and HLA-B allele group profiles for 31 Latin American populations and 61 ancestral populations from Iberia, Italy, Sub-Saharan Africa, and America. Results from population genetics comparisons show a wide variation in the HLA profiles from the Latin American populations that correlate with different admixture proportions. Populations in Latin America seem to be organized in at least three groups with (1) strong Amerindian admixture, (2) strong Caucasian component, and (3) a Caucasian-African gradient. These results imply that genetic risk assessment for HSCT in Latin America has to be adapted for different population subgroups rather than as a pan-Hispanic/Latino analysis.</p>","PeriodicalId":9220,"journal":{"name":"Bone Marrow Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/136087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31097422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 13
The Role of HLA in Cord Blood Transplantation. HLA 在脐带血移植中的作用。
Bone Marrow Research Pub Date : 2012-01-01 Epub Date: 2012-10-11 DOI: 10.1155/2012/485160
Catherine Stavropoulos-Giokas, Amalia Dinou, Andreas Papassavas
{"title":"The Role of HLA in Cord Blood Transplantation.","authors":"Catherine Stavropoulos-Giokas, Amalia Dinou, Andreas Papassavas","doi":"10.1155/2012/485160","DOIUrl":"10.1155/2012/485160","url":null,"abstract":"<p><p>In recent years, umbilical cord blood (CB), a rich source of hematopoietic stem cells (HSC), has been used successfully as an alternative HSC source to treat a variety of hematologic, immunologic, genetic, and oncologic disorders. CB has several advantages, including prompt availability of the transplant, decrease of graft versus host disease (GVHD) and better long-term immune recovery, resulting in a similar long-term survival. Studies have shown that some degree of HLA mismatches is acceptable. This review is intended to outline the main aspects of HLA matching in different settings (related, pediatric, adult, or double-unit HSCT), its effect on transplantation outcome and the role of HLA in donor selection.</p>","PeriodicalId":9220,"journal":{"name":"Bone Marrow Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31001532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Controversies and recent advances in hematopoietic cell transplantation for follicular non-hodgkin lymphoma. 造血细胞移植治疗滤泡性非霍奇金淋巴瘤的争议与最新进展。
Bone Marrow Research Pub Date : 2012-01-01 Epub Date: 2012-10-11 DOI: 10.1155/2012/897215
Abraham S Kanate, Mohamed A Kharfan-Dabaja, Mehdi Hamadani
{"title":"Controversies and recent advances in hematopoietic cell transplantation for follicular non-hodgkin lymphoma.","authors":"Abraham S Kanate,&nbsp;Mohamed A Kharfan-Dabaja,&nbsp;Mehdi Hamadani","doi":"10.1155/2012/897215","DOIUrl":"https://doi.org/10.1155/2012/897215","url":null,"abstract":"<p><p>Commonly designated as an indolent non-Hodgkin lymphoma, follicular lymphoma (FL) presents with striking pathobiological and clinical heterogeneity. Initial management strategies for FL have evolved to involve combination chemoimmunotherapy and/or radio-immunoconjugates. Unfortunately even with the best available nontransplant treatment, which nowadays results in higher frequency of response, FL remains incurable. Although considered a feasible therapeutic option, the use of hematopoietic cell transplantation (HCT) remains controversial. The appropriate timing, graft source, and intensity of HCT conditioning regimens in FL are often matters of debate. Herein we review the available published data pertaining to the use of autologous or allogeneic HCT in patients with FL across different stages of the disease, discuss major recent advances in the field, and highlight avenues for future research. The current literature does not support a role of HCT for FL in first remission, but in the relapsed setting autologous HCT remains appropriate for patients with early chemosensitive relapses, while allogeneic transplantation remains the sole curative modality for this disease, in relatively younger patients without significant comorbidities.</p>","PeriodicalId":9220,"journal":{"name":"Bone Marrow Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/897215","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31001533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
NOD2 Polymorphisms and Their Impact on Haematopoietic Stem Cell Transplant Outcome. NOD2多态性及其对造血干细胞移植结果的影响
Bone Marrow Research Pub Date : 2012-01-01 Epub Date: 2012-10-18 DOI: 10.1155/2012/180391
Neema P Mayor, Bronwen E Shaw, J Alejandro Madrigal, Steven G E Marsh
{"title":"NOD2 Polymorphisms and Their Impact on Haematopoietic Stem Cell Transplant Outcome.","authors":"Neema P Mayor,&nbsp;Bronwen E Shaw,&nbsp;J Alejandro Madrigal,&nbsp;Steven G E Marsh","doi":"10.1155/2012/180391","DOIUrl":"https://doi.org/10.1155/2012/180391","url":null,"abstract":"<p><p>Haematopoietic stem cell transplantation (HSCT) is a valuable tool in the treatment of many haematological disorders. Advances in understanding HLA matching have improved prognoses. However, many recipients of well-matched HSCT develop posttransplant complications, and survival is far from absolute. The pursuit of novel genetic factors that may impact on HSCT outcome has resulted in the publication of many articles on a multitude of genes. Three NOD2 polymorphisms, identified as disease-associated variants in Crohn's disease, have recently been suggested as important candidate gene markers in the outcome of HSCT. It was originally postulated that as the clinical manifestation of inflammatory responses characteristic of several post-transplant complications was of notable similarity to those seen in Crohn's disease, it was possible that they shared a common cause. Since the publication of this first paper, numerous studies have attempted to replicate the results in different transplant settings. The data has varied considerably between studies, and as yet no consensus on the impact of NOD2 SNPs on HSCT outcome has been achieved. Here, we will review the existing literature, summarise current theories as to why the data differs, and suggest possible mechanisms by which the SNPs affect HSCT outcome.</p>","PeriodicalId":9220,"journal":{"name":"Bone Marrow Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/180391","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31021722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 10
Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma without Cryopreservation. 自体造血干细胞移植治疗多发性骨髓瘤无冷冻保存。
Bone Marrow Research Pub Date : 2012-01-01 Epub Date: 2012-05-28 DOI: 10.1155/2012/917361
Khalid Ahmed Al-Anazi
{"title":"Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma without Cryopreservation.","authors":"Khalid Ahmed Al-Anazi","doi":"10.1155/2012/917361","DOIUrl":"https://doi.org/10.1155/2012/917361","url":null,"abstract":"<p><p>High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation is considered the standard of care for multiple myeloma patients who are eligible for transplantation. The process of autografting comprises the following steps: control of the primary disease by using a certain induction therapeutic protocol, mobilization of stem cells, collection of mobilized stem cells by apheresis, cryopreservation of the apheresis product, administration of high-dose pretransplant conditioning therapy, and finally infusion of the cryopreserved stem cells after thawing. However, in cancer centers that treat patients with multiple myeloma and have transplantation capabilities but lack or are in the process of acquiring cryopreservation facilities, alternatively noncryopreserved autologous stem cell therapy has been performed with remarkable success as the pretransplant conditioning therapy is usually brief.</p>","PeriodicalId":9220,"journal":{"name":"Bone Marrow Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/917361","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30687452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 24
The Presence of Anti-HLA Antibodies before and after Allogeneic Hematopoietic Stem Cells Transplantation from HLA-Mismatched Unrelated Donors. 来自hla不匹配非亲属供者的异基因造血干细胞移植前后hla抗体的存在。
Bone Marrow Research Pub Date : 2012-01-01 Epub Date: 2012-10-24 DOI: 10.1155/2012/539825
Anna Koclega, Miroslaw Markiewicz, Urszula Siekiera, Alicja Dobrowolska, Mizia Sylwia, Monika Dzierzak-Mietla, Patrycja Zielinska, Malgorzata Sobczyk Kruszelnicka, Andrzej Lange, Slawomira Kyrcz-Krzemien
{"title":"The Presence of Anti-HLA Antibodies before and after Allogeneic Hematopoietic Stem Cells Transplantation from HLA-Mismatched Unrelated Donors.","authors":"Anna Koclega,&nbsp;Miroslaw Markiewicz,&nbsp;Urszula Siekiera,&nbsp;Alicja Dobrowolska,&nbsp;Mizia Sylwia,&nbsp;Monika Dzierzak-Mietla,&nbsp;Patrycja Zielinska,&nbsp;Malgorzata Sobczyk Kruszelnicka,&nbsp;Andrzej Lange,&nbsp;Slawomira Kyrcz-Krzemien","doi":"10.1155/2012/539825","DOIUrl":"https://doi.org/10.1155/2012/539825","url":null,"abstract":"<p><p>Although anti-human leukocyte antigen antibodies (anti-HLA Abs) are important factors responsible for graft rejection in solid organ transplantation and play a role in post-transfusion complications, their role in allogeneic hematopoietic stem cell transplantation (allo-HSCT) has not been finally defined. Enormous polymorphism of HLA-genes, their immunogenicity and heterogeneity of antibodies, as well as the growing number of allo-HSCTs from partially HLA-mismatched donors, increase the probability that anti-HLA antibodies could be important factors responsible for the treatment outcomes. We have examined the incidence of anti-HLA antibodies in a group of 30 allo-HSCT recipients from HLA-mismatched unrelated donors. Anti-HLA Abs were identified in sera collected before and after allo-HSCT. We have used automated DynaChip assay utilizing microchips bearing purified class I and II HLA antigens for detection of anti-HLA Abs. We have detected anit-HLA antibodies against HLA-A, B, C, DR, DQ and DP, but no donor or recipient-specific anti-HLA Abs were detected in the studied group. The preliminary results indicate that anti-HLA antibodies are present before and after allo-HSCT in HLA-mismatched recipients.</p>","PeriodicalId":9220,"journal":{"name":"Bone Marrow Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/539825","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31045568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 12
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