全文获取类型
收费全文 | 931篇 |
免费 | 43篇 |
出版年
2023年 | 7篇 |
2022年 | 15篇 |
2021年 | 17篇 |
2020年 | 21篇 |
2019年 | 20篇 |
2018年 | 43篇 |
2017年 | 18篇 |
2016年 | 30篇 |
2015年 | 41篇 |
2014年 | 43篇 |
2013年 | 72篇 |
2012年 | 72篇 |
2011年 | 83篇 |
2010年 | 51篇 |
2009年 | 27篇 |
2008年 | 44篇 |
2007年 | 43篇 |
2006年 | 37篇 |
2005年 | 38篇 |
2004年 | 43篇 |
2003年 | 23篇 |
2002年 | 30篇 |
2001年 | 11篇 |
2000年 | 8篇 |
1999年 | 12篇 |
1998年 | 16篇 |
1997年 | 3篇 |
1996年 | 10篇 |
1995年 | 10篇 |
1994年 | 7篇 |
1993年 | 5篇 |
1992年 | 2篇 |
1991年 | 5篇 |
1990年 | 4篇 |
1989年 | 4篇 |
1988年 | 7篇 |
1987年 | 2篇 |
1986年 | 6篇 |
1985年 | 3篇 |
1982年 | 5篇 |
1981年 | 5篇 |
1980年 | 5篇 |
1979年 | 5篇 |
1977年 | 4篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1967年 | 2篇 |
1966年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有974条查询结果,搜索用时 15 毫秒
81.
Nikunj Mapara Mansi Sharma Varsha Shriram Renu Bharadwaj K. C. Mohite Vinay Kumar 《Applied microbiology and biotechnology》2015,99(24):10655-10667
82.
Shalindra Ranasinghe Renu Wickremasinghe Sanjeeva Hulangamuwa Ganga Sirimanna Nandimithra Opathella Rhaiza DC Maingon Vishvanath Chandrasekharan 《Memórias do Instituto Oswaldo Cruz》2015,110(8):1017-1023
Leishmania donovani is the known causative agent of both cutaneous
(CL) and visceral leishmaniasis in Sri Lanka. CL is considered to be under-reported
partly due to relatively poor sensitivity and specificity of microscopic diagnosis.
We compared robustness of three previously described polymerase chain reaction (PCR)
based methods to detectLeishmania DNA in 38 punch biopsy samples
from patients presented with suspected lesions in 2010. Both,
Leishmaniagenus-specific JW11/JW12 KDNA and LITSR/L5.8S internal
transcribed spacer (ITS)1 PCR assays detected 92% (35/38) of the samples whereas a
KDNA assay specific forL. donovani (LdF/LdR) detected only 71%
(27/38) of samples. All positive samples showed a L. donovani
banding pattern upon HaeIII ITS1 PCR-restriction fragment length polymorphism
analysis. PCR assay specificity was evaluated in samples containing
Mycobacterium tuberculosis, Mycobacterium
leprae, and human DNA, and there was no cross-amplification in JW11/JW12
and LITSR/L5.8S PCR assays. The LdF/LdR PCR assay did not amplify M.
leprae or human DNA although 500 bp and 700 bp bands were observed in
M. tuberculosis samples. In conclusion, it was successfully shown
in this study that it is possible to diagnose Sri Lankan CL with high accuracy, to
genus and species identification, using Leishmania DNA PCR
assays. 相似文献
83.
84.
Konstantin E. Komolov Anshul Bhardwaj Jeffrey L. Benovic 《The Journal of biological chemistry》2015,290(34):20629-20647
G protein-coupled receptor kinases (GRKs) are members of the protein kinase A, G, and C families (AGC) and play a central role in mediating G protein-coupled receptor phosphorylation and desensitization. One member of the family, GRK5, has been implicated in several human pathologies, including heart failure, hypertension, cancer, diabetes, and Alzheimer disease. To gain mechanistic insight into GRK5 function, we determined a crystal structure of full-length human GRK5 at 1.8 Å resolution. GRK5 in complex with the ATP analog 5′-adenylyl β,γ-imidodiphosphate or the nucleoside sangivamycin crystallized as a monomer. The C-terminal tail (C-tail) of AGC kinase domains is a highly conserved feature that is divided into three segments as follows: the C-lobe tether, the active-site tether (AST), and the N-lobe tether (NLT). This domain is fully resolved in GRK5 and reveals novel interactions with the nucleotide and N-lobe. Similar to other AGC kinases, the GRK5 AST is an integral part of the nucleotide-binding pocket, a feature not observed in other GRKs. The AST also mediates contact between the kinase N- and C-lobes facilitating closure of the kinase domain. The GRK5 NLT is largely displaced from its previously observed position in other GRKs. Moreover, although the autophosphorylation sites in the NLT are >20 Å away from the catalytic cleft, they are capable of rapid cis-autophosphorylation suggesting high mobility of this region. In summary, we provide a snapshot of GRK5 in a partially closed state, where structural elements of the kinase domain C-tail are aligned to form novel interactions to the nucleotide and N-lobe not previously observed in other GRKs. 相似文献
85.
Bhardwaj N Abyzov A Clarke D Shou C Gerstein MB 《Protein science : a publication of the Protein Society》2011,20(10):1745-1754
The integration of molecular networks with other types of data, such as changing levels of gene expression or protein-structural features, can provide richer information about interactions than the simple node-and-edge representations commonly used in the network community. For example, the mapping of 3D-structural data onto networks enables classification of proteins into singlish- or multi-interface hubs (depending on whether they have >2 interfaces). Similarly, interactions can be classified as permanent or transient, depending on whether their interface is used by only one or by multiple partners. Here, we incorporate an additional dimension into molecular networks: dynamic conformational changes. We parse the entire PDB structural databank for alternate conformations of proteins and map these onto the protein interaction network, to compile a first version of the Dynamic Structural Interaction Network (DynaSIN). We make this network available as a readily downloadable resource file, and we then use it to address a variety of downstream questions. In particular, we show that multi-interface hubs display a greater degree of conformational change than do singlish-interface ones; thus, they show more plasticity which perhaps enables them to utilize more interfaces for interactions. We also find that transient associations involve smaller conformational changes than permanent ones. Although this may appear counterintuitive, it is understandable in the following framework: as proteins involved in transient interactions shuttle between interchangeable associations, they interact with domains that are similar to each other and so do not require drastic structural changes for their activity. We provide evidence for this hypothesis through showing that interfaces involved in transient interactions bind fewer classes of domains than those in a control set. 相似文献
86.
87.
88.
Guarino LA Bhardwaj K Dong W Sun J Holzenburg A Kao C 《Journal of molecular biology》2005,353(5):1106-1117
The severe acute respiratory syndrome (SARS) coronavirus virus non-structural protein 15 is a Mn2+-dependent endoribonuclease with specificity for cleavage at uridylate residues. To better understand structural and functional characteristics of Nsp15, 22 mutant versions of Nsp15 were produced in Escherichia coli as His-tagged proteins and purified by metal-affinity and ion-exchange chromatography. Nineteen of the mutants were soluble and were analyzed for enzymatic activity. Six mutants, including four at the putative active site, were significantly reduced in endoribonuclease activity. Two of the inactive mutants had unusual secondary structures compared to the wild-type protein, as measured by circular dichroism spectroscopy. Gel-filtration analysis, velocity sedimentation ultracentrifugation, and native gradient pore electrophoresis all showed that the wild-type protein exists in an equilibrium between hexamers and monomers in solution, with hexamers dominating at micromolar protein concentration, while native gradient pore electrophoresis also revealed the presence of trimers. A mutant in the N terminus of Nsp15 was impaired in hexamer formation and had low endoribonuclease activity, suggesting that oligomerization is required for endoribonuclease activity. This idea was supported by titration experiments showing that enzyme activity was strongly concentration-dependent, indicating that oligomeric Nsp15 is the active form. Three-dimensional reconstruction of negatively stained single particles of Nsp15 viewed by transmission electron microscopic analysis suggested that the six subunits were arranged as a dimer of trimers with a number of cavities or channels that may constitute RNA binding sites. 相似文献
89.
90.
Tapas?K?BasakEmail author Suman?Halder Madona?Kumar Renu?Sharma Bijoylaxmi?Midya 《Theoretical biology & medical modelling》2005,2(1):11