全文获取类型
收费全文 | 18733篇 |
免费 | 1638篇 |
国内免费 | 1665篇 |
出版年
2024年 | 14篇 |
2023年 | 190篇 |
2022年 | 261篇 |
2021年 | 723篇 |
2020年 | 574篇 |
2019年 | 767篇 |
2018年 | 765篇 |
2017年 | 577篇 |
2016年 | 818篇 |
2015年 | 1226篇 |
2014年 | 1475篇 |
2013年 | 1459篇 |
2012年 | 1832篇 |
2011年 | 1719篇 |
2010年 | 1108篇 |
2009年 | 961篇 |
2008年 | 1219篇 |
2007年 | 1122篇 |
2006年 | 893篇 |
2005年 | 799篇 |
2004年 | 695篇 |
2003年 | 604篇 |
2002年 | 570篇 |
2001年 | 297篇 |
2000年 | 260篇 |
1999年 | 227篇 |
1998年 | 153篇 |
1997年 | 114篇 |
1996年 | 73篇 |
1995年 | 59篇 |
1994年 | 58篇 |
1993年 | 37篇 |
1992年 | 58篇 |
1991年 | 45篇 |
1990年 | 43篇 |
1989年 | 35篇 |
1988年 | 26篇 |
1987年 | 19篇 |
1986年 | 20篇 |
1985年 | 20篇 |
1984年 | 13篇 |
1983年 | 11篇 |
1982年 | 11篇 |
1979年 | 13篇 |
1978年 | 6篇 |
1976年 | 5篇 |
1975年 | 9篇 |
1974年 | 8篇 |
1970年 | 4篇 |
1968年 | 4篇 |
排序方式: 共有10000条查询结果,搜索用时 234 毫秒
1.
2.
Peng Wang Ronghua Luo Min Zhang Yaqing Wang Tianzhang Song Tingting Tao Zhongyu Li Lin Jin Hongyi Zheng Wenwen Chen Mengqian Zhao Yongtang Zheng Jianhua Qin 《Cell death & disease》2020,11(12)
COVID-19, caused by SARS-CoV-2, is an acute and rapidly developing pandemic, which leads to a global health crisis. SARS-CoV-2 primarily attacks human alveoli and causes severe lung infection and damage. To better understand the molecular basis of this disease, we sought to characterize the responses of alveolar epithelium and its adjacent microvascular endothelium to viral infection under a co-culture system. SARS-CoV-2 infection caused massive virus replication and dramatic organelles remodeling in alveolar epithelial cells, alone. While, viral infection affected endothelial cells in an indirect manner, which was mediated by infected alveolar epithelium. Proteomics analysis and TEM examinations showed viral infection caused global proteomic modulations and marked ultrastructural changes in both epithelial cells and endothelial cells under the co-culture system. In particular, viral infection elicited global protein changes and structural reorganizations across many sub-cellular compartments in epithelial cells. Among the affected organelles, mitochondrion seems to be a primary target organelle. Besides, according to EM and proteomic results, we identified Daurisoline, a potent autophagy inhibitor, could inhibit virus replication effectively in host cells. Collectively, our study revealed an unrecognized cross-talk between epithelium and endothelium, which contributed to alveolar–capillary injury during SARS-CoV-2 infection. These new findings will expand our understanding of COVID-19 and may also be helpful for targeted drug development.Subject terms: Mechanisms of disease, Viral infection 相似文献
3.
4.
To determine whether the bicyclic monoterpene olefins (-)-alpha-pinene and (-)-beta-pinene arise biosynthetically from the same monoterpene cyclase by alternate deprotonations of a common carbocationic intermediate, the product distributions arising from the acyclic precursor [10-2H3,1-3H]geranyl pyrophosphate were compared with those resulting from incubation of [1-3H]geranyl pyrophosphate with (-)-pinene cyclase from Salvia officinalis. Alteration in proportions of the olefinic products generated by the partially purified pinene cyclase resulted from the suppression of the formation of (-)-beta-pinene (C10 deprotonation) by a primary deuterium isotope effect with a compensating stimulation of the formation of (-)-alpha-pinene (C4 deprotonation). (-)-Pinene cyclase as well as (+)-pinene cyclase also exhibited a decrease in the proportion of the acyclic olefin myrcene generated from the deuteriated substrate, accompanied by a corresponding increase in the commitment to cyclized products. The observation of isotopically sensitive branching, in conjunction with quantitation of the magnitude of the secondary deuterium isotope effect on the overall rate of product formation by the (+)- and (-)-pinene cyclases as well as two other monoterpene cyclases from the same tissue, supports the biosynthetic origin of (-)-alpha-pinene and (-)-beta-pinene by alternative deprotonations of a common enzymatic intermediate. A biogenetic scheme consistent with these results is presented, and alternate proposals for the origin of the pinenes are addressed. 相似文献
5.
6.
Yihao Yang Ziyan Shen Youguang Li Chenda Xu Han Xia Hao Zhuang Shengyuan Sun Min Guo Changjie Yan 《植物学报(英文版)》2022,64(10):1860-1865
Rice eating and cooking quality (ECQ) is a major concern of breeders and consumers, determining market competitiveness worldwide. Rice grain protein content (GPC) is negatively related to ECQ, making it possible to improve ECQ by manipulating GPC. However, GPC is genetically complex and sensitive to environmental conditions; therefore, little progress has been made in traditional breeding for ECQ. Here, we report that CRISPR/Cas9-mediated knockout of genes encoding the grain storage protein glutelin rapidly produced lines with downregulated GPC and improved ECQ. Our finding provides a new strategy for improving rice ECQ. 相似文献
7.
8.
9.
10.
Ryan K. Cheu Andrew T. Gustin Christina Lee Luca Schifanella Charlene J. Miller Avie Ha Casey Kim Violeta J. Rodriguez Margaret Fischl Adam D. Burgener Kelly B. Arnold Maria L. Alcaide Nichole R. Klatt 《PLoS pathogens》2020,16(12)
Despite the efficacy of antiretroviral-based pre-exposure prophylactics (PrEP) in men who have sex with men, studies in women have produced widely varying outcomes. Recent evidence demonstrates that vaginal microbial communities are associated with increased HIV acquisition risk and may impact PrEP efficacy. Here, we investigate the mechanisms underlying how vaginal bacteria alter PrEP drug levels and impact HIV infection rates ex vivo. Using cervicovaginal lavages (CVLs) from women with or without bacterial vaginosis (BV), we identified microbial metabolism of PrEP drugs in BV samples through LC-MS/MS analysis of soluble drug levels and metabolite formation in dual T-cell cultures. CVL samples were assessed for microbiome analysis using sequencing of bacterial 16S rRNA genes. We also observed non-Lactobacillus bacteria that are associated with BV may potentially impact PrEP efficacy through increased HIV infection rates in co-cultures containing Lactobacillus or BV bacteria, PrEP drugs, CEM-GFP cells, and HIV-1LAI virus. Finally, we used these data to develop a novel predictive mathematical simulation modeling system to predict these drug interactions for future trials. These studies demonstrate how dysbiotic vaginal microbiota may impact PrEP drugs and provides evidence linking vaginal bacteria to PrEP efficacy in women. 相似文献