全文获取类型
收费全文 | 7400篇 |
免费 | 470篇 |
国内免费 | 276篇 |
出版年
2024年 | 3篇 |
2023年 | 90篇 |
2022年 | 154篇 |
2021年 | 200篇 |
2020年 | 164篇 |
2019年 | 193篇 |
2018年 | 290篇 |
2017年 | 146篇 |
2016年 | 153篇 |
2015年 | 184篇 |
2014年 | 511篇 |
2013年 | 532篇 |
2012年 | 304篇 |
2011年 | 439篇 |
2010年 | 486篇 |
2009年 | 549篇 |
2008年 | 554篇 |
2007年 | 554篇 |
2006年 | 490篇 |
2005年 | 416篇 |
2004年 | 338篇 |
2003年 | 308篇 |
2002年 | 269篇 |
2001年 | 132篇 |
2000年 | 114篇 |
1999年 | 97篇 |
1998年 | 118篇 |
1997年 | 72篇 |
1996年 | 44篇 |
1995年 | 52篇 |
1994年 | 48篇 |
1993年 | 36篇 |
1992年 | 25篇 |
1991年 | 9篇 |
1990年 | 11篇 |
1989年 | 8篇 |
1988年 | 6篇 |
1987年 | 4篇 |
1986年 | 5篇 |
1985年 | 6篇 |
1984年 | 3篇 |
1983年 | 6篇 |
1982年 | 7篇 |
1981年 | 6篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 3篇 |
1973年 | 1篇 |
排序方式: 共有8146条查询结果,搜索用时 31 毫秒
91.
Wenfei Ding Hui Yin Tan Jia Xiang Zhang Luke A. Wilczek Karin R. Hsieh Jeffrey A. Mulkin Piero R. Bianco 《Protein science : a publication of the Protein Society》2020,29(5):1211-1227
The Escherichia coli single‐strand DNA binding protein (SSB) is essential to viability where it functions to regulate SSB interactome function. Here it binds to single‐stranded DNA and to target proteins that comprise the interactome. The region of SSB that links these two essential protein functions is the intrinsically disordered linker. Key to linker function is the presence of three, conserved PXXP motifs that mediate binding to oligosaccharide‐oligonucleotide binding folds (OB‐fold) present in SSB and its interactome partners. Not surprisingly, partner OB‐fold deletions eliminate SSB binding. Furthermore, single point mutations in either the PXXP motifs or, in the RecG OB‐fold, obliterate SSB binding. The data also demonstrate that, and in contrast to the view currently held in the field, the C‐terminal acidic tip of SSB is not required for interactome partner binding. Instead, we propose the tip has two roles. First, and consistent with the proposal of Dixon, to regulate the structure of the C‐terminal domain in a biologically active conformation that prevents linkers from binding to SSB OB‐folds until this interaction is required. Second, as a secondary binding domain. Finally, as OB‐folds are present in SSB and many of its partners, we present the SSB interactome as the first family of OB‐fold genome guardians identified in prokaryotes. 相似文献
92.
《Bioorganic & medicinal chemistry》2020,28(20):115711
Cyclic peptides are capable of binding to challenging targets (e.g., proteins involved in protein-protein interactions) with high affinity and specificity, but generally cannot gain access to intracellular targets because of poor membrane permeability. In this work, we discovered a conformationally constrained cyclic cell-penetrating peptide (CPP) containing a d-Pro-l-Pro motif, cyclo(AFΦrpPRRFQ) (where Φ is l-naphthylalanine, r is d-arginine, and p is d-proline). The structural constraints provided by cyclization and the d-Pro-l-Pro motif permitted the rational design of cell-permeable cyclic peptides of large ring sizes (up to 16 amino acids). This strategy was applied to design a potent, cell-permeable, and biologically active cyclic peptidyl inhibitor, cyclo(YpVNFΦrpPRR) (where Yp is l-phosphotyrosine), against the Grb2 SH2 domain. Multidimensional NMR spectroscopic and circular dichroism analyses revealed that the cyclic CPP as well as the Grb2 SH2 inhibitor assume a predominantly random coil structure but have significant β-hairpin character surrounding the d-Pro-l-Pro motif. These results demonstrate cyclo(AFΦrpPRRFQ) as an effective CPP for endocyclic (insertion of cargo into the CPP ring) or exocyclic delivery of biological cargos (attachment of cargo to the Gln side chain). 相似文献
93.
94.
[背景] S蛋白是猪流行性腹泻病毒(Porcine Epidemic Diarrhea Virus,PEDV)的主要结构蛋白和免疫原性蛋白,在前期的研究中,本课题组在S蛋白的胞内区鉴定到2个包含线性B细胞表位的短肽。[目的] 鉴定PEDV S蛋白胞内区线性B细胞表位的最小基序。[方法] 原核表达2个短肽的每次后移1个氨基酸的系列8肽,以兔抗S蛋白血清为一抗,通过Western Blot筛选阳性反应8肽,鉴定S蛋白胞内区线性B细胞表位的最小基序。[结果] S蛋白胞内区的2个包含线性B细胞表位的短肽共享一个表位,该表位的最小基序为1371QPYE1374。同源性分析显示该B细胞表位基序为保守性表位。[结论] 确定了S蛋白胞内区线性B细胞表位的最小基序为1371QPYE1374;S蛋白抗原表位的鉴定有助于提高对其结构和功能的理解。 相似文献
95.
Kunitz型丝氨酸蛋白酶抑制剂是一类普遍存在的蛋白酶抑制剂,在体内各项生命活动中扮演着重要角色。这类抑制剂结构稳定且富有特色,通常具有一个或几个串联存在的Kunitz结构域,能够以类似底物的方式与丝氨酸蛋白酶结合,从而抑制酶的活性。在功能方面,Kunitz型丝氨酸蛋白酶抑制剂参与凝血和纤维蛋白溶解、肿瘤免疫、炎症调节以及抵抗细菌、真菌感染等过程。文中就Kunitz型丝氨酸蛋白酶抑制剂研究进展作一综述,为新型Kunitz型丝氨酸蛋白酶抑制剂的开发提供研究思路。 相似文献
96.
97.
98.
The DM9 domain is a protein unit of 60–75 amino acids that has been first detected in the fruit fly Drosophila as a repeated motif of unknown function. Recent research on proteins carrying DM9 domains in the mosquito Anopheles gambiae and the oyster Crassostrea gigas indicated an association with the uptake of microbial organisms. Likewise, in the trematode Fasciola gigantica DM9-1 showed intracellular relocalization following microbial, heat and drug stress. In the present research, we show that FgDM9-1 is a lectin with a novel mannose-binding site that has been recently described for the protein CGL1 of Crassostrea gigas. This property allowed FgDM9-1 to agglutinate gram-positive and -negative bacteria with appropriate cell surface glycosylation patterns. Furthermore, FgDM9-1 caused hemagglutination across all ABO blood group phenotypes. It is speculated that the parenchymal located FgDM9-1 has a role in cellular processes that involve the transport of mannose-carrying molecules in the parenchymal cells of the parasite. 相似文献
99.
Virologica Sinica - Ebola virus (EBOV) belongs to the Filoviridae family and causes severe illnesses such as hemorrhagic fever with a high mortality rate up to 90%. Now two antibody drugs termed... 相似文献
100.
Li Jiang-Fan He Lei Deng Yong-Qiang Qi Shu-Hui Chen Yue-Hong Zhang Xiao-Lu Hu Shi-Xiong Fan Rui-Wen Zhao Guang-Yu Qin Cheng-Feng 《中国病毒学》2021,36(6):1484-1491
Virologica Sinica - The sudden emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) has caused global panic in 2003, and the risk of SARS-CoV outbreak still exists. However, no... 相似文献