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Segmental Isotope Labeling of the Prion Protein: Identification of a Key Residue for Copper-Mediated Interdomain Structure. 朊病毒蛋白的片段同位素标记:铜介导的结构域间结构关键残基的鉴定。
IF 3.5 2区 生物学
ACS Chemical Biology Pub Date : 2025-07-24 DOI: 10.1021/acschembio.5c00336
Francesca A Pavlovici, Kevin Singewald, Samuel Kaplan, Eefei Chen, Glenn L Millhauser
{"title":"Segmental Isotope Labeling of the Prion Protein: Identification of a Key Residue for Copper-Mediated Interdomain Structure.","authors":"Francesca A Pavlovici, Kevin Singewald, Samuel Kaplan, Eefei Chen, Glenn L Millhauser","doi":"10.1021/acschembio.5c00336","DOIUrl":"https://doi.org/10.1021/acschembio.5c00336","url":null,"abstract":"<p><p>The cellular prion protein is composed of two domains: a disordered N-terminal toxic effector domain and a three-helix C-terminal regulatory domain. Copper is thought to form a bridge between these two domains, inhibiting the protein's inherent neurotoxicity. However, the molecular details of how copper interacts with the C-terminal regulatory surface are unclear. To assess the potential role of conserved C-terminal His residues in copper coordination, we applied sortase-mediated ligation to create an expressed murine prion protein with segmental <sup>15</sup>N-labeling of the N-terminal domain. Pulsed EPR methods applied to a 1:1 protein:copper complex revealed both <sup>14</sup>N and <sup>15</sup>N couplings, consistent with simultaneous coordination of the two proteins' domains to the copper center. Mutagenesis studies localized C-terminal copper coordination to His176, present on the second α-helix. The cumulative EPR results reveal a copper coordination environment composed of three His residues from the protein's N-terminal domain, along with His176. The feasibility of these findings was tested with AlphaFold 3 simulations. These results further refine the molecular details of the prion protein's autoregulation, emphasizing the critical role of its copper cofactor. Moreover, this interdisciplinary work demonstrates how sortase-mediated ligation combined with pulsed EPR sensitive to distinct nuclear spin systems provides a new strategy for assessing metal ion binding to proteins.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Origin of the Different Binding Affinities of (9R)- and (9S)-Hexahydrocannabinol (HHC) for the CB1 and CB2 Cannabinoid Receptors. (9R)-和(9S)-六氢大麻酚(HHC)对CB1和CB2大麻素受体的不同结合亲和力的来源
IF 3.5 2区 生物学
ACS Chemical Biology Pub Date : 2025-07-24 DOI: 10.1021/acschembio.5c00399
Pan-Pan Chen, Meng Duan, Qingyang Zhou, Fang Liu, Yi Tang, Neil K Garg, K N Houk
{"title":"Origin of the Different Binding Affinities of (9<i>R</i>)- and (9<i>S</i>)-Hexahydrocannabinol (HHC) for the CB<sub>1</sub> and CB<sub>2</sub> Cannabinoid Receptors.","authors":"Pan-Pan Chen, Meng Duan, Qingyang Zhou, Fang Liu, Yi Tang, Neil K Garg, K N Houk","doi":"10.1021/acschembio.5c00399","DOIUrl":"https://doi.org/10.1021/acschembio.5c00399","url":null,"abstract":"<p><p>Hexahydrocannabinols (HHCs) are emerging cannabinoids that have become available for recreational use and were recently classified as Schedule II under an international treaty. Although often advertised for having desirable effects, recent studies have shown that commercial products typically contain variable amounts of two epimers, (9<i>R</i>)-HHC and (9<i>S</i>)-HHC. In turn, these epimers have been shown to have different binding affinities to the CB<sub>1</sub> and CB<sub>2</sub> receptors. We report a computational study that interrogates the origins of these differing affinities. Molecular docking and molecular dynamics simulations were employed to investigate the binding of (9<i>R</i>)-HHC and (9<i>S</i>)-HHC to cannabinoid receptors CB<sub>1</sub> and CB<sub>2</sub>. Computational results show key binding interactions and highlight important conformational effects. For both receptors, the (9<i>R</i>)-HHC isomer exists primarily in a chair conformation, placing the C9 methyl substituent in a favorable equatorial position in the active sites. However, (9<i>S</i>)-HHC exists in equilibrium between the chair and twist-boat conformations within the receptor's active site, ultimately leading to less favorable binding in the CB<sub>1</sub> and CB<sub>2</sub> active sites, making (9<i>S</i>)-HHC a less favorable ligand compared to (9<i>R</i>)-HHC. These studies explain the relative binding of HHCs and are expected to enable the investigation of other cannabinoids that display improved or selective receptor binding.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neutral pH-Selective Inhibition of Cytosolic Cathepsin B: A Novel Drug Targeting Strategy for Traumatic Brain Injury and Alzheimer's Disease. 中性ph选择性抑制胞质组织蛋白酶B:创伤性脑损伤和阿尔茨海默病的新药物靶向策略。
IF 3.5 2区 生物学
ACS Chemical Biology Pub Date : 2025-07-23 DOI: 10.1021/acschembio.5c00463
Vivian Hook, Sonia Podvin, Michael C Yoon, Von V Phan, Jazmin Florio, Brian Spencer, Charles Mosier, Adeline Cheng, Sarah Ahuett, Jehad Almaliti, William H Gerwick, Robert A Rissman, Anthony J O'Donoghue
{"title":"Neutral pH-Selective Inhibition of Cytosolic Cathepsin B: A Novel Drug Targeting Strategy for Traumatic Brain Injury and Alzheimer's Disease.","authors":"Vivian Hook, Sonia Podvin, Michael C Yoon, Von V Phan, Jazmin Florio, Brian Spencer, Charles Mosier, Adeline Cheng, Sarah Ahuett, Jehad Almaliti, William H Gerwick, Robert A Rissman, Anthony J O'Donoghue","doi":"10.1021/acschembio.5c00463","DOIUrl":"https://doi.org/10.1021/acschembio.5c00463","url":null,"abstract":"<p><p>Cathepsin B contributes to the behavioral deficits and neuropathology that occur in traumatic brain injury (TBI) and Alzheimer's disease (AD). TBI and AD patients display elevated levels of cathepsin B that correlate with the severity of injury or cognitive deficits, respectively. In animal models of TBI and AD, cathepsin B gene knockout ameliorates behavioral deficits and improves neuropathology. While cathepsin B is normally located in acidic lysosomes, during TBI and AD, lysosomal leakage results in the translocation of cathepsin B to the neutral pH environment of the cytosol, thereby initiating neurodegeneration. Neutral pH-selective inhibitors are hypothesized to specifically target the pathogenic cytosolic cathepsin B without affecting its normal lysosomal form. Therefore, this review focuses on a novel strategy to utilize pH-dependent substrate cleavage properties of cathepsin B for the design of a neutral pH-selective inhibitor. Investigation of the enzymatic properties of cathepsin B at different pH conditions led to the development of Z-Arg-Lys-AOMK, a neutral pH-selective inhibitor that does not affect the enzyme's activity at normal lysosomal acidic pH. Z-Arg-Lys-AOMK potently inhibits cathepsin B at nM concentrations and effectively inhibits cellular cathepsin B in neuronal cell cultures at similar levels. In mice subjected to controlled cortical impact (CCI) brain injury, a model of TBI, cytosolic cathepsin B activity was significantly elevated in the brain. Treatment of the CCI-TBI mice with Z-Arg-Lys-AOMK reduced cytosolic cathepsin B activity and resulted in less motor dysfunction. These findings show that pH-dependent cleavage properties of cathepsin B can be utilized for the development of selective inhibitors to target the neutral cytosolic form of cathepsin B. The new concept of pH-selective inhibitors of cathepsin B reveals novel opportunities for targeting pathogenic, cytosolic cathepsin B involved in brain disorders.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Seven Cyclization Patterns of Type II PKS Yield Fluorescent Compounds, Including Fungal-Type Folded Globismycin A. II型PKS的7种环化模式产生荧光化合物,包括真菌型折叠环球霉素A。
IF 3.5 2区 生物学
ACS Chemical Biology Pub Date : 2025-07-21 DOI: 10.1021/acschembio.5c00299
Wenjuan Ding, Yuliang Dong, Run Xu, Dong Liang, Xiaolin Yuan, Le Zhou, Changli Sun, Huaran Zhang, Minyong Li, Junying Ma, Jianhua Ju, Qinglian Li
{"title":"Seven Cyclization Patterns of Type II PKS Yield Fluorescent Compounds, Including Fungal-Type Folded Globismycin A.","authors":"Wenjuan Ding, Yuliang Dong, Run Xu, Dong Liang, Xiaolin Yuan, Le Zhou, Changli Sun, Huaran Zhang, Minyong Li, Junying Ma, Jianhua Ju, Qinglian Li","doi":"10.1021/acschembio.5c00299","DOIUrl":"https://doi.org/10.1021/acschembio.5c00299","url":null,"abstract":"<p><p>Aromatic polyketides have emerged as an important source of fluorescent natural products, which hold significant value for research and diagnostic applications. In this study, we reported the discovery of three new (<b>5</b>, <b>6</b>, and <b>9</b>) and ten known (<b>1</b>-<b>4</b>, <b>7</b>, <b>8</b>, and <b>10</b>-<b>13</b>) fluorescent aromatic polyketides representing seven sets of carbon skeletons. Compounds <b>3</b>-<b>13</b> exhibited fluorescence ranging from cyan to orange-yellow and displayed varied behaviors in terms of excitation wavelength, emission wavelength, and Stokes shift, indicating their diverse spectral characteristics and environmental responsiveness. Notably, globismycin A (<b>5</b>) features an unprecedented 2,3-dihydrobenzofuro[4,5,6-de]chromene scaffold. Compound <b>5</b> not only exhibited high quantum yields in both water and organic solvents, with visible green fluorescence to the naked eye, but also showed potent selective cytotoxicity against three cancer cell lines. Biosynthetic investigations through a combination of gene inactivation, heterologous expression, and <sup>13</sup>C-labeled acetate feeding studies revealed that these fluorescent compounds, despite differing in size and shape, are all derived from a type II polyketide synthase (PKS) gene cluster <i>sgl</i>, and their diverse skeletons are generated through seven distinct cyclization patterns. More importantly, compound <b>5</b> uniquely involves a characteristic fungal F-mode first-ring cyclization step, although <b>5</b> has been proven to be a bacterial aromatic polyketide. These findings not only provide excellent fluorescent candidates potentially useful for various biological applications but also expand our understanding on the biosynthetic mechanisms driving the production of diverse aromatic polyketides by type II gene clusters.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Disrupting the Base Excision Repair (BER) Pathway by Targeting the Abasic Site Enhances the Sensitivity of PARP Inhibitor in HR-Proficient Cancer Cells. 靶向基础位点破坏碱基切除修复(BER)通路可增强PARP抑制剂在hr精通癌细胞中的敏感性
IF 3.5 2区 生物学
ACS Chemical Biology Pub Date : 2025-07-21 DOI: 10.1021/acschembio.5c00022
Achyut Bora, Bhim Majhi, Subhadeep Palit, Rounak Patra, Sanjay Dutta
{"title":"Disrupting the Base Excision Repair (BER) Pathway by Targeting the Abasic Site Enhances the Sensitivity of PARP Inhibitor in HR-Proficient Cancer Cells.","authors":"Achyut Bora, Bhim Majhi, Subhadeep Palit, Rounak Patra, Sanjay Dutta","doi":"10.1021/acschembio.5c00022","DOIUrl":"https://doi.org/10.1021/acschembio.5c00022","url":null,"abstract":"<p><p>Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) are clinically effective in homologous recombination (HR)-deficient cancers but have limited efficacy in HR-proficient cancers; therefore, new strategies are needed to address this therapeutic limitation. Since PARP1 recognizes abasic sites as intermediates to repair single-strand breaks (SSBs) in the base excision repair (BER) pathway, we demonstrate that targeting these DNA abasic sites with a fused-quinoxaline-diazepine amine derivative (<b>BA-6</b>) can enhance the effectiveness of the PARPi Olaparib in HR-proficient cancer cells (MDA-MB-231, HeLa, and SKOV3). <b>BA-6</b> cleaves abasic sites via β- and β,δ-elimination mechanisms, generating unusable substrates for DNA polymerase β, such as 3'-α,β<i>-</i>unsaturated aldehyde and 3'-phosphate products, thereby disrupting the BER pathway and leading to the accumulation of SSBs. Upon combination with a low micromolar dosage of Olaparib, <b>BA-6</b> exhibited potent synergistic effects in HR-proficient cancer cells by reducing cell viability and clonogenic survival. Interestingly, the following synergy is attributed to PARP trapping at <b>BA-6</b>-induced SSBs, leading to DNA double-strand breaks (DSBs) during replication, as evidenced by an increased comet tail length and γH2AX expression, ultimately inducing S-phase arrest and apoptosis in HR-proficient cancer cells. Furthermore, combining <b>BA-6</b> with alkylating agents like Temozolomide (TMZ) and methylmethanesulfonate (MMS), which elevate abasic sites, remarkably increased the Olaparib potency (∼55-fold) in HR-proficient cancer cells. Overall, this study established that targeting DNA abasic sites with diazepine hybrids such as <b>BA-6</b>, in combination with known PARPi, acts as a rational strategy to enhance the therapeutic efficacy even in HR-proficient cancers.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
IF 3.5 2区 生物学
ACS Chemical Biology Pub Date : 2025-07-18
Magdalena Niemczura, Aleksi Nuutila, Rongbin Wang, Katariina Rauhanen, S. Eric Nybo and Mikko Metsä-Ketelä*, 
{"title":"","authors":"Magdalena Niemczura,&nbsp;Aleksi Nuutila,&nbsp;Rongbin Wang,&nbsp;Katariina Rauhanen,&nbsp;S. Eric Nybo and Mikko Metsä-Ketelä*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 7","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.5,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acschembio.5c00205","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144646169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
IF 3.5 2区 生物学
ACS Chemical Biology Pub Date : 2025-07-18
Minsoo Kim, Kwangho Kim, Jesun Lee, Lea A. Barny, Toya D. Scaggs, Ian M. Romaine, KyuOk Jeon, Simona G. Codreanu, Stacy D. Sherrod, John A. McLean, Anjaparavanda P. Naren, Gary A. Sulikowski and Lars Plate*, 
{"title":"","authors":"Minsoo Kim,&nbsp;Kwangho Kim,&nbsp;Jesun Lee,&nbsp;Lea A. Barny,&nbsp;Toya D. Scaggs,&nbsp;Ian M. Romaine,&nbsp;KyuOk Jeon,&nbsp;Simona G. Codreanu,&nbsp;Stacy D. Sherrod,&nbsp;John A. McLean,&nbsp;Anjaparavanda P. Naren,&nbsp;Gary A. Sulikowski and Lars Plate*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 7","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.5,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acschembio.5c00157","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144646170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
IF 3.5 2区 生物学
ACS Chemical Biology Pub Date : 2025-07-18
Taku Tsukidate, Ansuman Sahoo, Geetanjali Pendyala, Rong-Sheng Yang, Jonathan Welch, Sri Madabhushi* and Xuanwen Li*, 
{"title":"","authors":"Taku Tsukidate,&nbsp;Ansuman Sahoo,&nbsp;Geetanjali Pendyala,&nbsp;Rong-Sheng Yang,&nbsp;Jonathan Welch,&nbsp;Sri Madabhushi* and Xuanwen Li*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 7","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.5,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acschembio.5c00081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144646187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
IF 3.5 2区 生物学
ACS Chemical Biology Pub Date : 2025-07-18
{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 7","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.5,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/cbv020i007_1960834","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144646191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction to "Thiophenyl Derivatives of Nicotinamide Are Metabolized by the NAD Salvage Pathway into Unnatural NAD Derivatives That Inhibit IMPDH and Are Toxic to Peripheral Nerve Cancers". 更正“烟酰胺的噻吩基衍生物通过NAD修复途径代谢成非天然的NAD衍生物,抑制IMPDH并对周围神经肿瘤有毒”。
IF 3.5 2区 生物学
ACS Chemical Biology Pub Date : 2025-07-18 Epub Date: 2025-06-30 DOI: 10.1021/acschembio.5c00436
Panayotis C Theodoropoulos, Holly H Guo, Wentian Wang, Eric Crossley, Giomar Rivera Cancel, Min Fang, Thu Nguyen, Hamid Baniasadi, Noelle S Williams, Joseph M Ready, Jef K De Brabander, Deepak Nijhawan
{"title":"Correction to \"Thiophenyl Derivatives of Nicotinamide Are Metabolized by the NAD Salvage Pathway into Unnatural NAD Derivatives That Inhibit IMPDH and Are Toxic to Peripheral Nerve Cancers\".","authors":"Panayotis C Theodoropoulos, Holly H Guo, Wentian Wang, Eric Crossley, Giomar Rivera Cancel, Min Fang, Thu Nguyen, Hamid Baniasadi, Noelle S Williams, Joseph M Ready, Jef K De Brabander, Deepak Nijhawan","doi":"10.1021/acschembio.5c00436","DOIUrl":"10.1021/acschembio.5c00436","url":null,"abstract":"","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":"1813"},"PeriodicalIF":3.5,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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