全文获取类型
收费全文 | 1014篇 |
免费 | 55篇 |
国内免费 | 1篇 |
出版年
2023年 | 6篇 |
2022年 | 5篇 |
2021年 | 25篇 |
2020年 | 18篇 |
2019年 | 25篇 |
2018年 | 27篇 |
2017年 | 28篇 |
2016年 | 31篇 |
2015年 | 54篇 |
2014年 | 49篇 |
2013年 | 69篇 |
2012年 | 75篇 |
2011年 | 77篇 |
2010年 | 44篇 |
2009年 | 36篇 |
2008年 | 61篇 |
2007年 | 54篇 |
2006年 | 52篇 |
2005年 | 39篇 |
2004年 | 42篇 |
2003年 | 43篇 |
2002年 | 32篇 |
2001年 | 15篇 |
2000年 | 14篇 |
1999年 | 11篇 |
1998年 | 4篇 |
1997年 | 7篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1992年 | 4篇 |
1990年 | 5篇 |
1985年 | 4篇 |
1984年 | 7篇 |
1983年 | 5篇 |
1980年 | 6篇 |
1979年 | 6篇 |
1978年 | 3篇 |
1977年 | 5篇 |
1891年 | 5篇 |
1890年 | 2篇 |
1885年 | 2篇 |
1883年 | 5篇 |
1879年 | 2篇 |
1877年 | 5篇 |
1876年 | 3篇 |
1874年 | 4篇 |
1873年 | 5篇 |
1872年 | 7篇 |
1871年 | 2篇 |
1870年 | 3篇 |
排序方式: 共有1070条查询结果,搜索用时 15 毫秒
71.
Lysis of human immunodeficiency virus type 1 by a specific secreted human phospholipase A2 下载免费PDF全文
Kim JO Chakrabarti BK Guha-Niyogi A Louder MK Mascola JR Ganesh L Nabel GJ 《Journal of virology》2007,81(3):1444-1450
Phospholipase A2 (PLA2) proteins affect cellular activation, signal transduction, and possibly innate immunity. A specific secretory PLA2, sPLA2-X, is shown here to neutralize human immunodeficiency virus type 1 (HIV-1) through degradation of the viral membrane. Catalytic function was required for antiviral activity, and the target cells of infection were unaffected. sPLA2-X potently reduced gene transfer of HIV-1 Env-pseudotyped lentivirus vectors and inhibited the replication of both CCR5- and CXCR4-tropic HIV-1 in human CD4+ T cells. Virions resistant to damage by antibody and complement were sensitive to lysis by sPLA2-X, suggesting a novel mechanism of antiviral surveillance independent of the acquired immune system. 相似文献
72.
Lad Y Kiema T Jiang P Pentikäinen OT Coles CH Campbell ID Calderwood DA Ylänne J 《The EMBO journal》2007,26(17):3993-4004
Human filamins are large actin-crosslinking proteins composed of an N-terminal actin-binding domain followed by 24 Ig-like domains (IgFLNs), which interact with numerous transmembrane receptors and cytosolic signaling proteins. Here we report the 2.5 A resolution structure of a three-domain fragment of human filamin A (IgFLNa19-21). The structure reveals an unexpected domain arrangement, with IgFLNa20 partially unfolded bringing IgFLNa21 into close proximity to IgFLNa19. Notably the N-terminus of IgFLNa20 forms a beta-strand that associates with the CD face of IgFLNa21 and occupies the binding site for integrin adhesion receptors. Disruption of this IgFLNa20-IgFLNa21 interaction enhances filamin binding to integrin beta-tails. Structural and functional analysis of other IgFLN domains suggests that auto-inhibition by adjacent IgFLN domains may be a general mechanism controlling filamin-ligand interactions. This can explain the increased integrin binding of filamin splice variants and provides a mechanism by which ligand binding might impact filamin structure. 相似文献
73.
Aruliah Rajasekar Thambidurai Ganesh Babu Sundaram Maruthamuthu Shunmugiah Thevar Karutha Pandian Sidhan Mohanan Narayanan Palaniswamy 《World journal of microbiology & biotechnology》2007,23(8):1065-1074
A facultative anaerobic species Serratia marcescens ACE2 isolated from the corrosion products of a diesel-transporting pipeline in North West India was identified by 16S rDNA
sequence analysis. The role of Serratia marcesens ACE2 on biodegradation of commercial corrosion inhibitor (CCI) and its influence on the corrosion of API 5LX steel has been
enlightened. The degrading strain ACE2 is involved in the process of corrosion of steel API 5LX and also utilizes the inhibitor
as organic source. The quantitative biodegradation efficiency of corrosion inhibitor was 58%, which was calculated by gas
chromatography mass spectrum analysis. The effect of CCI on the growth of bacteria and its corrosion inhibition efficiency
were investigated. Additionally, the role of this bacterium in corrosion of steel has been investigated by powder X-ray diffractometer
(XRD) and scanning electron microscope studies. The presence of high-intensity ferric oxides and manganese oxides noticed
from the XRD indicates that ACE2 enhances the corrosion process in presence of inhibitor as a carbon source. This basic study
will be useful for the development of new approaches for the detection, monitoring and control of microbial corrosion in petroleum
product pipelines. 相似文献
74.
In prokaryotes, DNA replication is initiated by the binding of DnaA to the oriC region of the chromosome to load the primosome machinery and start a new replication round. Several proteins control these events in Escherichia coli to ensure that replication is precisely timed during the cell cycle. Here, we report the crystal structure of HobA (HP1230) at 1.7 A, a recently discovered protein that specifically interacts with DnaA protein from Helicobacter pylori (HpDnaA). We found that the closest structural homologue of HobA is a sugar isomerase (SIS) domain containing protein, the phosphoheptose isomerase from Pseudomonas aeruginosa. Remarkably, SIS proteins share strong sequence homology with DiaA from E. coli; yet, HobA and DiaA share no sequence homology. Thus, by solving the structure of HobA, we unexpectedly discovered that HobA is a H. pylori structural homologue of DiaA. By comparing the structure of HobA to a homology model of DiaA, we identified conserved, surface-accessible residues that could be involved in protein-protein interaction. Finally, we show that HobA specifically interacts with the N-terminal part of HpDnaA. The structural homology between DiaA and HobA strongly supports their involvement in the replication process and these proteins could define a new structural family of replication regulators in bacteria. 相似文献
75.
Cho K Agrawal GK Shibato J Jung YH Kim YK Nahm BH Jwa NS Tamogami S Han O Kohda K Iwahashi H Rakwal R 《Journal of proteome research》2007,6(9):3581-3603
76.
77.
78.
79.
80.
An integrative approach combining ion mobility mass spectrometry,X-ray crystallography,and nuclear magnetic resonance spectroscopy to study the conformational dynamics of α1-antitrypsin upon ligand binding 下载免费PDF全文
Mun Peak Nyon Tanya Prentice Jemma Day John Kirkpatrick Ganesh N Sivalingam Geraldine Levy Imran Haq James A Irving David A Lomas John Christodoulou Bibek Gooptu Konstantinos Thalassinos 《Protein science : a publication of the Protein Society》2015,24(8):1301-1312
Native mass spectrometry (MS) methods permit the study of multiple protein species within solution equilibria, whereas ion mobility (IM)-MS can report on conformational behavior of specific states. We used IM-MS to study a conformationally labile protein (α1-antitrypsin) that undergoes pathological polymerization in the context of point mutations. The folded, native state of the Z-variant remains highly polymerogenic in physiological conditions despite only minor thermodynamic destabilization relative to the wild-type variant. Various data implicate kinetic instability (conformational lability within a native state ensemble) as the basis of Z α1-antitrypsin polymerogenicity. We show the ability of IM-MS to track such disease-relevant conformational behavior in detail by studying the effects of peptide binding on α1-antitrypsin conformation and dynamics. IM-MS is, therefore, an ideal platform for the screening of compounds that result in therapeutically beneficial kinetic stabilization of native α1-antitrypsin. Our findings are confirmed with high-resolution X-ray crystallographic and nuclear magnetic resonance spectroscopic studies of the same event, which together dissect structural changes from dynamic effects caused by peptide binding at a residue-specific level. IM-MS methods, therefore, have great potential for further study of biologically relevant thermodynamic and kinetic instability of proteins and provide rapid and multidimensional characterization of ligand interactions of therapeutic interest.PDB Code(s): 4PYW 相似文献