全文获取类型
收费全文 | 654篇 |
免费 | 58篇 |
专业分类
712篇 |
出版年
2022年 | 4篇 |
2021年 | 4篇 |
2020年 | 4篇 |
2019年 | 6篇 |
2018年 | 8篇 |
2017年 | 9篇 |
2016年 | 10篇 |
2015年 | 19篇 |
2014年 | 23篇 |
2013年 | 30篇 |
2012年 | 44篇 |
2011年 | 44篇 |
2010年 | 20篇 |
2009年 | 17篇 |
2008年 | 34篇 |
2007年 | 32篇 |
2006年 | 20篇 |
2005年 | 30篇 |
2004年 | 31篇 |
2003年 | 29篇 |
2002年 | 27篇 |
2001年 | 18篇 |
2000年 | 10篇 |
1999年 | 14篇 |
1998年 | 14篇 |
1997年 | 6篇 |
1995年 | 9篇 |
1994年 | 10篇 |
1993年 | 5篇 |
1992年 | 11篇 |
1991年 | 10篇 |
1990年 | 7篇 |
1989年 | 7篇 |
1988年 | 5篇 |
1987年 | 9篇 |
1986年 | 10篇 |
1985年 | 10篇 |
1984年 | 8篇 |
1983年 | 11篇 |
1982年 | 8篇 |
1981年 | 7篇 |
1980年 | 14篇 |
1979年 | 8篇 |
1977年 | 7篇 |
1976年 | 6篇 |
1974年 | 4篇 |
1972年 | 5篇 |
1970年 | 4篇 |
1969年 | 3篇 |
1966年 | 3篇 |
排序方式: 共有712条查询结果,搜索用时 15 毫秒
41.
Reducing the computational complexity of protein folding via fragment folding and assembly
下载免费PDF全文
![点击此处可从《Protein science : a publication of the Protein Society》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Haspel N Tsai CJ Wolfson H Nussinov R 《Protein science : a publication of the Protein Society》2003,12(6):1177-1187
Understanding, and ultimately predicting, how a 1-D protein chain reaches its native 3-D fold has been one of the most challenging problems during the last few decades. Data increasingly indicate that protein folding is a hierarchical process. Hence, the question arises as to whether we can use the hierarchical concept to reduce the practically intractable computational times. For such a scheme to work, the first step is to cut the protein sequence into fragments that form local minima on the polypeptide chain. The conformations of such fragments in solution are likely to be similar to those when the fragments are embedded in the native fold, although alternate conformations may be favored during the mutual stabilization in the combinatorial assembly process. Two elements are needed for such cutting: (1) a library of (clustered) fragments derived from known protein structures and (2) an assignment algorithm that selects optimal combinations to "cover" the protein sequence. The next two steps in hierarchical folding schemes, not addressed here, are the combinatorial assembly of the fragments and finally, optimization of the obtained conformations. Here, we address the first step in a hierarchical protein-folding scheme. The input is a target protein sequence and a library of fragments created by clustering building blocks that were generated by cutting all protein structures. The output is a set of cutout fragments. We briefly outline a graph theoretic algorithm that automatically assigns building blocks to the target sequence, and we describe a sample of the results we have obtained. 相似文献
42.
43.
Remodeling of the actin cytoskeleton during mammalian sperm capacitation and acrosome reaction 总被引:7,自引:0,他引:7
Brener E Rubinstein S Cohen G Shternall K Rivlin J Breitbart H 《Biology of reproduction》2003,68(3):837-845
The sperm acrosome reaction and penetration of the egg follow zona pellucida binding only if the sperm has previously undergone the poorly understood maturation process known as capacitation. We demonstrate here that in vitro capacitation of bull, ram, mouse, and human sperm was accompanied by a time-dependent increase in actin polymerization. Induction of the acrosome reaction in capacitated cells initiated fast F-actin breakdown. Incubation of sperm in media lacking BSA or methyl-beta-cyclodextrin, Ca(2+), or NaHCO(3), components that are all required for capacitation, prevented actin polymerization as well as capacitation, as assessed by the ability of the cells to undergo the acrosome reaction. Inhibition of F-actin formation by cytochalasin D blocked sperm capacitation and reduced the in vitro fertilization rate of metaphase II-arrested mouse eggs. It has been suggested that protein tyrosine phosphorylation may represent an important regulatory pathway that is associated with sperm capacitation. We show here that factors known to stimulate sperm protein tyrosine phosphorylation (i.e., NaHCO(3), cAMP, epidermal growth factor, H(2)O(2), and sodium vanadate) were able to enhance actin polymerization, whereas inhibition of tyrosine kinases prevented F-actin formation. These data suggest that actin polymerization may represent an important regulatory pathway in with sperm capacitation, whereas F-actin breakdown occurs before the acrosome reaction. 相似文献
44.
Summary . Suppose that the true model underlying a set of data is one of a finite set of candidate models, and that parameter estimation for this model is of primary interest. With this goal, optimal design must depend on a loss function across all possible models. A common method that accounts for model uncertainty is to average the loss over all models; this is the basis of what is known as Läuter's criterion. We generalize Läuter's criterion and show that it can be placed in a Bayesian decision theoretic framework, by extending the definition of Bayesian A‐optimality. We use this generalized A‐optimality to find optimal design points in an environmental safety setting. In estimating the smallest detectable trace limit in a water contamination problem, we obtain optimal designs that are quite different from those suggested by standard A‐optimality. 相似文献
45.
Lindzen M Aizman R Lifshitz Y Lubarski I Karlish SJ Garty H 《The Journal of biological chemistry》2003,278(21):18738-18743
Corticosteroid hormone-induced factor (CHIF) and the gamma subunit of the Na,K-ATPase (gamma) are two members of the FXYD family whose function has been elucidated recently. CHIF and gamma interact with the Na+ pump and alter its kinetic properties, in different ways, which appear to serve their specific physiological roles. Although functional interactions with the Na,K-ATPase have been clearly demonstrated, it is not known which domains and which residues interact with the alpha and/or beta subunits and affect the pump kinetics. The current study provides the first systematic analysis of structure-function relations of CHIF and gamma. It is demonstrated that the stability of detergent-solubilized complexes of CHIF and gamma with alpha and/or beta subunits is determined by the trans-membrane segments, especially three residues that may be involved in hydrophobic interactions. The transmembrane segments also determine the opposite effects of CHIF and gamma on the Na+ affinity of the pump, but the amino acids involved in this functional effect are different from those responsible for stable interactions with alpha. 相似文献
46.
A novel founder mutation in the RNASEL gene, 471delAAAG,is associated with prostate cancer in Ashkenazi Jews 总被引:7,自引:0,他引:7
Rennert H Bercovich D Hubert A Abeliovich D Rozovsky U Bar-Shira A Soloviov S Schreiber L Matzkin H Rennert G Kadouri L Peretz T Yaron Y Orr-Urtreger A 《American journal of human genetics》2002,71(4):981-984
HPC1/RNASEL was recently identified as a candidate gene for hereditary prostate cancer. We identified a novel founder frameshift mutation in RNASEL, 471delAAAG, in Ashkenazi Jews. The mutation frequency in the Ashkenazi population, estimated on the basis of the frequency in 150 healthy young women, was 4% (95% confidence interval [CI] 1.9%-8.4%). Among Ashkenazi Jews, the mutation frequency was higher in patients with prostate cancer (PRCA) than in elderly male control individuals (6.9% vs. 2.4%; odds ratio = 3.0; 95% CI 0.6-15.3; P=.17). 471delAAAG was not detected in the 134 non-Ashkenazi patients with PRCA and control individuals tested. The median age at PRCA diagnosis did not differ significantly between the Ashkenazi carriers and noncarriers included in our study. However, carriers received diagnoses at a significantly earlier age, compared with patients with PRCA who were registered in the Israeli National Cancer Registry (65 vs. 74.4 years, respectively; P<.001). When we examined two brothers with PRCA, we found a heterozygous 471delAAAG mutation in one and a homozygous mutation in the other. Loss of heterozygosity was demonstrated in the tumor of the heterozygous sib. Taken together, these data suggest that the 471delAAAG null mutation is associated with PRCA in Ashkenazi men. However, additional studies are required to determine whether this mutation confers increased risk for PRCA in this population. 相似文献
47.
Béguin P Crambert G Monnet-Tschudi F Uldry M Horisberger JD Garty H Geering K 《The EMBO journal》2002,21(13):3264-3273
Recently, corticosteroid hormone-induced factor (CHIF) and the gamma-subunit, two members of the FXYD family of small proteins, have been identified as regulators of renal Na,K-ATPase. In this study, we have investigated the tissue distribution and the structural and functional properties of FXYD7, another family member which has not yet been characterized. Expressed exclusively in the brain, FXYD7 is a type I membrane protein bearing N-terminal, post-translationally added modifications on threonine residues, most probably O-glycosylations that are important for protein stabilization. Expressed in Xenopus oocytes, FXYD7 can interact with Na,K-ATPase alpha 1-beta 1, alpha 2-beta 1 and alpha 3-beta 1 but not with alpha-beta 2 isozymes, whereas, in brain, it is only associated with alpha 1-beta isozymes. FXYD7 decreases the apparent K(+) affinity of alpha 1-beta 1 and alpha 2-beta 1, but not of alpha 3-beta1 isozymes. These data suggest that FXYD7 is a novel, tissue- and isoform-specific Na,K-ATPase regulator which could play an important role in neuronal excitability. 相似文献
48.
49.
The docking field has come of age. The time is ripe to present the principles of docking, reviewing the current state of the field. Two reasons are largely responsible for the maturity of the computational docking area. First, the early optimism that the very presence of the "correct" native conformation within the list of predicted docked conformations signals a near solution to the docking problem, has been replaced by the stark realization of the extreme difficulty of the next scoring/ranking step. Second, in the last couple of years more realistic approaches to handling molecular flexibility in docking schemes have emerged. As in folding, these derive from concepts abstracted from statistical mechanics, namely, populations. Docking and folding are interrelated. From the purely physical standpoint, binding and folding are analogous processes, with similar underlying principles. Computationally, the tools developed for docking will be tremendously useful for folding. For large, multidomain proteins, domain docking is probably the only rational way, mimicking the hierarchical nature of protein folding. The complexity of the problem is huge. Here we divide the computational docking problem into its two separate components. As in folding, solving the docking problem involves efficient search (and matching) algorithms, which cover the relevant conformational space, and selective scoring functions, which are both efficient and effectively discriminate between native and non-native solutions. It is universally recognized that docking of drugs is immensely important. However, protein-protein docking is equally so, relating to recognition, cellular pathways, and macromolecular assemblies. Proteins function when they are bound to other molecules. Consequently, we present the review from both the computational and the biological points of view. Although large, it covers only partially the extensive body of literature, relating to small (drug) and to large protein-protein molecule docking, to rigid and to flexible. Unfortunately, when reviewing these, a major difficulty in assessing the results is the non-uniformity in the formats in which they are presented in the literature. Consequently, we further propose a way to rectify it here. 相似文献
50.