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121.
122.
Insights into the potential function and membrane organization of the TP0435 (Tp17) lipoprotein from Treponema pallidum derived from structural and biophysical analyses 下载免费PDF全文
Chad A. Brautigam Ranjit K. Deka Wei Z. Liu Michael V. Norgard 《Protein science : a publication of the Protein Society》2015,24(1):11-19
The sexually transmitted disease syphilis is caused by the bacterial spirochete Treponema pallidum. This microorganism is genetically intractable, accounting for the large number of putative and undercharacterized members of the pathogen's proteome. In an effort to ascribe a function(s) to the TP0435 (Tp17) lipoprotein, we engineered a soluble variant of the protein (rTP0435) and determined its crystal structure at a resolution of 2.42 Å. The structure is characterized by an eight‐stranded β‐barrel protein with a shallow “basin” at one end of the barrel and an α‐helix stacked on the opposite end. Furthermore, there is a disulfide‐linked dimer of the protein in the asymmetric unit of the crystals. Solution hydrodynamic experiments established that purified rTP0435 is monomeric, but specifically forms the disulfide‐stabilized dimer observed in the crystal structure. The data herein, when considered with previous work on TP0435, imply plausible roles for the protein in either ligand binding, treponemal membrane architecture, and/or pathogenesis. 相似文献
123.
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
124.
Moon DK Tripathi A Sullivan D Siegler MA Parkin S Posner GH 《Bioorganic & medicinal chemistry letters》2011,21(9):2773-2775
Four 5-carbon-linked trioxane dimer orthoesters (6a-6d) have been prepared in 4 or 5 chemical steps from the natural trioxane artemisinin (1). When administered orally to malaria-infected mice using a single dose of only 6 mg/kg body weight along with 18 mg/kg of mefloquine hydrochloride, trioxane dimer orthoester sulfone 6d completely and safely cured the mice; after 30 days, the cured mice showed no detectable parasitemia, gained at least as much weight as the control mice (no infection), and behaved normally. 相似文献
125.
Rowbottom DP 《Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences》2011,42(2):145-154
This paper, which is based on recent empirical research at the University of Leeds, the University of Edinburgh, and the University of Bristol, presents two difficulties which arise when condensed matter physicists interact with molecular biologists: (1) the former use models which appear to be too coarse-grained, approximate and/or idealized to serve a useful scientific purpose to the latter; and (2) the latter have a rather narrower view of what counts as an experiment, particularly when it comes to computer simulations, than the former. It argues that these findings are related; that computer simulations are considered to be undeserving of experimental status, by molecular biologists, precisely because of the idealizations and approximations that they involve. The complexity of biological systems is a key factor. The paper concludes by critically examining whether the new research programme of 'systems biology' offers a genuine alternative to the modelling strategies used by physicists. It argues that it does not. 相似文献
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127.
分布在蛋白质分子表面的暴露于溶剂的氨基酸所具有的一些特性对蛋白质的折叠和聚合过程、蛋白质一蛋白质相互作用以及蛋白质的功能具有重要影响。本文分析了蛋白质表面氨基酸在疏水性、保守性、静电势及结构方面的一些特性,阐述了近年来国际上利用这些特性对蛋白质一蛋白质相互作用界面进行预测的方法,最后介绍了几款预测蛋白质表面氨基酸的软件。 相似文献
128.
Meirmans PG 《Molecular ecology resources》2011,11(1):146-150
MARLIN is a software to create, run, analyse, and visualize spatially explicit population genetic simulations. It provides an intuitive user interface with which the geographical layout of a metapopulation can be drawn by hand or loaded from a map. Furthermore, the interface allows easy selection of the many different simulation settings. MARLIN then uses the program QuantiNemo to run the simulation in the background. When simulations are finished, MARLIN directly analyses and plots the results, thereby greatly simplifying the simulation workflow. This combination of simulation and analysis makes MARLIN ideal for teaching and for scientists who are interested in doing simulations without having to learn command-line operations. MARLIN is available for computers running Mac OS X and can be downloaded from: http://www.patrickmeirmans.com/software. 相似文献
129.
The hydrogeology between the catchment area and the divided dystrophic Lake Fuchskuhle with respect to the genesis and the land-water interactions were investigated. Water levels at numerous locations in the catchment area were measured in order to characterize the hydrology. The water balance of the area was calculated based on long term climatic investigations. The geology of the peat was documented at 25 sampling points by cores collected with a peat drill. Chemical parameters including pH, total phosphorus and total nitrogen concentrations, DOC concentration, colour (SAK 436 m–1) and the UV254/DOC ratio in the catchment area and in two compartments (NE and SW compartment) were determined. The chemical fluxes of DOC, nitrogen and phosphorus from the catchment area into one compartment (SW compartment) were determined. During the genesis of the Lake Fuchskuhle area two aquifer systems (local peat aquifer, regional sandy main aquifer) developed. Both aquifers are largely independently with almost no lateral interactions. Two compartments are supplied with water from the local peat aquifer. From the other two compartments, however, water is flowing out into the peat body. During high groundwater inflow into the SW compartment higher concentration of DOC, nitrogen and phosphorus in the SW compartment were detected. The fen can be divided in two parts: in the meso — to eutrophic fen northwest and the mainly meso — to oligotrophic — acid fen in the southeast. The significant differences in parameters such as pH, conductivity and DOC concentration gave a clear picture of the heterogeneity of the two compartments and their dependence on the catchment area with the two aquifers. 相似文献
130.
Kuroita T Matsumura H Yokota N Kitabayashi M Hashimoto H Inoue T Imanaka T Kai Y 《Journal of molecular biology》2005,351(2):291-298
A novel mechanism for controlling the proofreading and polymerase activities of archaeal DNA polymerases was studied. The 3'-5'exonuclease (proofreading) activity and PCR performance of the family B DNA polymerase from Thermococcus kodakaraensis KOD1 (previously Pyrococcus kodakaraensis KOD1) were altered efficiently by mutation of a "unique loop" in the exonuclease domain. Interestingly, eight different H147 mutants showed considerable variations in respect to their 3'-5'exonuclease activity, from 9% to 276%, as against that of the wild-type (WT) enzyme. We determined the 2.75A crystal structure of the H147E mutant of KOD DNA polymerase that shows 30% of the 3'-5'exonuclease activity, excellent PCR performance and WT-like fidelity. The structural data indicate that the properties of the H147E mutant were altered by a conformational change of the Editing-cleft caused by an interaction between the unique loop and the Thumb domain. Our data suggest that electrostatic and hydrophobic interactions between the unique loop of the exonuclease domain and the tip of the Thumb domain are essential for determining the properties of these DNA polymerases. 相似文献