全文获取类型
收费全文 | 1368篇 |
免费 | 39篇 |
国内免费 | 46篇 |
专业分类
1453篇 |
出版年
2023年 | 11篇 |
2022年 | 37篇 |
2021年 | 17篇 |
2020年 | 27篇 |
2019年 | 32篇 |
2018年 | 26篇 |
2017年 | 30篇 |
2016年 | 22篇 |
2015年 | 52篇 |
2014年 | 95篇 |
2013年 | 120篇 |
2012年 | 124篇 |
2011年 | 79篇 |
2010年 | 45篇 |
2009年 | 84篇 |
2008年 | 101篇 |
2007年 | 68篇 |
2006年 | 65篇 |
2005年 | 57篇 |
2004年 | 53篇 |
2003年 | 55篇 |
2002年 | 32篇 |
2001年 | 9篇 |
2000年 | 10篇 |
1999年 | 18篇 |
1998年 | 18篇 |
1997年 | 11篇 |
1996年 | 9篇 |
1995年 | 14篇 |
1994年 | 6篇 |
1993年 | 8篇 |
1992年 | 9篇 |
1991年 | 9篇 |
1990年 | 8篇 |
1989年 | 4篇 |
1988年 | 5篇 |
1987年 | 11篇 |
1986年 | 2篇 |
1985年 | 10篇 |
1984年 | 16篇 |
1983年 | 8篇 |
1982年 | 11篇 |
1981年 | 3篇 |
1980年 | 7篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1976年 | 1篇 |
1973年 | 2篇 |
1972年 | 3篇 |
1971年 | 1篇 |
排序方式: 共有1453条查询结果,搜索用时 15 毫秒
961.
The properties of hemoproteins strictly depend on the type and orientation of axial ligands. Here, the orientations of axially coordinated His in bis-His complexes and the heme geometry in protein data bank have been analyzed. The effect of the bis-histidyl formation on the heme cavity of Antarctic fish hemoglobins has been also evaluated. The results show that protein matrix exerts a major effect on the conformation of axially ligated histidines: the imidazoles in bis-His complexes occupy a preferred relative orientation in globins and in model systems, whereas they adopt a variety of relative orientations in other hemoproteins. The bis-histidyl adducts affect the heme geometry inducing larger distortions from planarity with respect to other ligands. These deviations are larger in bis-His multiheme cytochromes than in globins. In Antarctic fish hemoglobins the bis-histidyl adduct adopts preferentially a distorted coordination and the formation of the bis-His complex induces a slight but significant modification in the shape, area and volume of the heme cavity. 相似文献
962.
David J. Harvey Anthony H. Merry Louise Royle Matthew P. Campbell Raymond A. Dwek Pauline M. Rudd 《Proteomics》2009,9(15):3796-3801
Symbolic diagrams are commonly used to depict N‐ and O‐linked glycans but there is no general consensus as to how individual constituent monosaccharides or linkages are shown. This article proposes a system that avoids ambiguities inherent in most other systems and is appropriate for both hand drawing and computer applications. Constituent monosaccharides are depicted by shapes modified to show OAc, deoxy, etc. Linkage is indicated by the bond angle and anomericity by solid (β) or dashed (α) lines. 相似文献
963.
A comprehensive understanding of protein–protein interactions is an important next step in our quest to understand how the information contained in a genome is put into action. Although a number of experimental techniques can report on the existence of a protein– protein interaction, very few can provide detailed structural information. NMR spectroscopy is one of these, and in recent years several complementary NMR approaches, including residual dipolar couplings and the use of paramagnetic effects, have been developed that can provide insight into the structure of protein–protein complexes. In this article, we review these approaches and comment on their strengths and weaknesses. 相似文献
964.
Many eukaryotic proteins exist in large multisubunit assemblies and often show compromised folding or activity when their
interaction partners are not present. Protein complexes in eukaryotes can contain ten or more subunits with individual polypeptides
ranging in size up to several hundred kilodalton, severely restricting the application of conventional cloning strategies
and imposing constraints on the choice of the expression host. Modern structural molecular biology often depends on introducing
diversity into the specimens under investigation, including mutation, truncation and placement of purification aids. Current
recombinant expression methods often require a disproportionate labor investment prior to multiprotein expression, and subsequent
to expression and analysis do not provide for rapid revision of the experiment. We have developed reagents and protocols for
rapid and flexible multiprotein complex expressions suitable for structural biology, focusing on multigene baculoviral vectors
and their recombination mediated assembly. A top priority in protein science is automation. Our strategy can be readily adapted
in a robotics setup, for baculovirus/insect cell expression of protein complexes, but likewise also for mammalian or prokaryotic
hosts. 相似文献
965.
Hans-Michael Kaltenbach 《FEBS letters》2009,583(24):3923-29
Besides the often-quoted complexity of cellular networks, the prevalence of uncertainties about components, interactions, and their quantitative features provides a largely underestimated hallmark of current systems biology. This uncertainty impedes the development of mechanistic mathematical models to achieve a true systems-level understanding. However, there is increasing evidence that theoretical approaches from diverse scientific domains can extract relevant biological knowledge efficiently, even from poorly characterized biological systems. As a common denominator, the methods focus on structural, rather than more detailed, kinetic network properties. A deeper understanding, better scaling, and the ability to combine the approaches pose formidable challenges for future theory developments. 相似文献
966.
A theoretical analysis of the distinguishability problem of two rival models of the single enzyme-single substrate reaction, the Michaelis-Menten and Henri mechanisms, is presented. We also outline a general approach for analysing the structural indistinguishability between two mechanisms. The approach involves constructing, if possible, a smooth mapping between the two candidate models. Evans et al. [N.D. Evans, M.J. Chappell, M.J. Chapman, K.R. Godfrey, Structural indistinguishability between uncontrolled (autonomous) nonlinear analytic systems, Automatica 40 (2004) 1947-1953] have shown that if, in addition, either of the mechanisms satisfies a particular criterion then such a transformation always exists when the models are indistinguishable from their experimentally observable outputs. The approach is applied to the single enzyme-single substrate reaction mechanism. In principle, mechanisms can be distinguished using this analysis, but we show that our ability to distinguish mechanistic models depends both on the precise measurements made, and on our knowledge of the system prior to performing the kinetics experiments. 相似文献
967.
A comprehensive structural analysis of interactions involving amide NH and C=O groups in protein-ligand complexes has been performed based on 3,275 published crystal structures (resolution < or =2.5 A). Most of the amide C=O and NH groups at the protein-ligand interface are highly buried within the binding site and involved in H-bonds with corresponding counter-groups. Small percentages of C=O and NH groups are solvated or embedded in hydrophobic environments. In particular, C=O groups show a higher propensity to be solvated or embedded in a hydrophobic environment than NH groups do. A small percentage of carbonyl groups is involved in weak hydrogen bonds with CH. Cases of dipolar interactions, involving carbonyl oxygen and electrophilic carbon atoms, such as amide, amidinium, guanidium groups, are also identified. A higher percentage of NH are in contact with aromatic carbons, interacting either through hydrogen bonds (preferably with the NH group pointing towards a ring carbon atom) or through stacking between amide plane and ring plane. Comprehensive studies such as the present one are thought to be important for future improvements in the molecular design area, in particular for the development of new scoring functions. [Figure: see text]. 相似文献
968.
Kamata T Handa M Ito S Sato Y Ohtani T Kawai Y Ikeda Y Aiso S 《The Journal of biological chemistry》2010,285(49):38428-38437
Integrins are postulated to undergo structural rearrangement from a low affinity bent conformer to a high affinity extended conformer upon activation. However, some reports have shown that a bent conformer is capable of binding a ligand, whereas another report has shown that integrin extension does not absolutely lead to activation. To clarify whether integrin affinity is indeed regulated by the so-called switchblade-like movement, we have engineered a series of mutant αIIbβ3 integrins that are constrained specifically in either a bent or an extended conformation. These mutant αIIbβ3 integrins were expressed in mammalian cells, and fibrinogen binding to these cells was examined. The bent integrins were created through the introduction of artificial disulfide bridges in the β-head/β-tail interface. Cells expressing bent integrins all failed to bind fibrinogen unless pretreated with DTT to disrupt the disulfide bridges. The extended integrins were created by introducing N-glycosylation sites in amino acid residues located close to the α-genu, where the integrin legs fold backward. Among these mutants, activation was maximized in one integrin with an N-glycosylation site located behind the α-genu. This extension-induced activation was completely blocked when the swing-out of the hybrid domain was prevented. These results suggest that the bent and extended conformers represent low affinity and high affinity conformers, respectively, and that extension-induced activation depends on the swing-out of the hybrid domain. Taken together, these results are consistent with the current hypothesis that integrin affinity is regulated by the switchblade-like movement of the integrin legs. 相似文献
969.
Marco Soriani Pierre Petit Renata Grifantini Roberto Petracca Giovanni Gancitano Elisabetta Frigimelica Filomena Nardelli Christel Garcia Silvia Spinelli Guido Scarabelli Sebastien Fiorucci Roman Affentranger Mario Ferrer-Navarro Martin Zacharias Giorgio Colombo Laurent Vuillard Xavier Daura Guido Grandi 《The Journal of biological chemistry》2010,285(39):30126-30138
We present an interdisciplinary approach that, by incorporating a range of experimental and computational techniques, allows the identification and characterization of functional/immunogenic domains. This approach has been applied to ArtJ, an arginine-binding protein whose orthologs in Chlamydiae trachomatis (CT ArtJ) and pneumoniae (CPn ArtJ) are shown to have different immunogenic properties despite a high sequence similarity (60% identity). We have solved the crystallographic structures of CT ArtJ and CPn ArtJ, which are found to display a type II transporter fold organized in two α-β domains with the arginine-binding region at their interface. Although ArtJ is considered to belong to the periplasm, we found that both domains contain regions exposed on the bacterial surface. Moreover, we show that recombinant ArtJ binds to epithelial cells in vitro, suggesting a role for ArtJ in host-cell adhesion during Chlamydia infection. Experimental epitope mapping and computational analysis of physicochemical determinants of antibody recognition revealed that immunogenic epitopes reside mainly in the terminal (D1) domain of both CPn and CT ArtJ, whereas the surface properties of the respective binding-prone regions appear sufficiently different to assume divergent immunogenic behavior. Neutralization assays revealed that sera raised against CPn ArtJ D1 partially reduce both CPn and CT infectivity in vitro, suggesting that functional antibodies directed against this domain may potentially impair chlamydial infectivity. These findings suggest that the approach presented here, combining functional and structure-based analyses of evolutionary-related antigens can be a valuable tool for the identification of cross-species immunogenic epitopes for vaccine development. 相似文献
970.
We report here the backbone assignment of Rv1567c, an integral membrane protein from Mycobacterium tuberculosis. The backbone resonance assignments were determined based on triple-resonance experiments with uniformly [13C,15N]-labeled protein in LMPG detergent micelles. 相似文献