全文获取类型
收费全文 | 755篇 |
免费 | 74篇 |
专业分类
829篇 |
出版年
2023年 | 3篇 |
2022年 | 3篇 |
2021年 | 13篇 |
2020年 | 4篇 |
2019年 | 5篇 |
2018年 | 8篇 |
2017年 | 12篇 |
2016年 | 11篇 |
2015年 | 17篇 |
2014年 | 34篇 |
2013年 | 32篇 |
2012年 | 54篇 |
2011年 | 46篇 |
2010年 | 29篇 |
2009年 | 25篇 |
2008年 | 33篇 |
2007年 | 24篇 |
2006年 | 38篇 |
2005年 | 25篇 |
2004年 | 27篇 |
2003年 | 19篇 |
2002年 | 24篇 |
2001年 | 24篇 |
2000年 | 22篇 |
1999年 | 23篇 |
1998年 | 21篇 |
1997年 | 14篇 |
1996年 | 10篇 |
1995年 | 13篇 |
1994年 | 10篇 |
1993年 | 12篇 |
1992年 | 20篇 |
1991年 | 31篇 |
1990年 | 11篇 |
1989年 | 10篇 |
1988年 | 14篇 |
1987年 | 19篇 |
1986年 | 9篇 |
1985年 | 6篇 |
1984年 | 8篇 |
1983年 | 4篇 |
1982年 | 3篇 |
1981年 | 4篇 |
1980年 | 9篇 |
1979年 | 10篇 |
1978年 | 5篇 |
1977年 | 10篇 |
1976年 | 4篇 |
1975年 | 4篇 |
1974年 | 3篇 |
排序方式: 共有829条查询结果,搜索用时 15 毫秒
41.
Garcia-Viloca M Poulsen TD Truhlar DG Gao J 《Protein science : a publication of the Protein Society》2004,13(9):2341-2354
A subject of great practical importance that has not received much attention is the question of the sensitivity of molecular dynamics simulations to the initial X-ray structure used to set up the calculation. We have found two cases in which seemingly similar structures lead to quite different results, and in this article we present a detailed analysis of these cases. The first case is acyl-CoA dehydrogenase, and the chief difference of the two structures is attributed to a slight shift in a backbone carbonyl that causes a key residue (the proton-abstracting base) to be in a bad conformation for reaction. The second case is xylose isomerase, and the chief difference of the two structures appears to be the ligand sphere of a Mg2+ metal cofactor that plays an active role in catalysis. 相似文献
42.
The crystallographic three-dimensional structure of the Escherichia coli maa gene product, previously identified as a maltose O-acetyltransferase (MAT) [Brand, B., and Boos, W. (1991) J. Biol. Chem. 266, 14113-14118] has been determined to 2.15 A resolution by the single anomalous dispersion method using data from a crystal cocrystallized with trimethyllead acetate. It is shown here that MAT acetylates glucose exclusively at the C6 position and maltose at the C6 position of the nonreducing end glucosyl moiety. Furthermore, MAT shows higher affinity toward artificial substrates containing an alkyl or hydrophobic chain as well as a glucosyl unit. The presence of a long hydrophobic patch near the acceptor site provides the structural explanation for this preference. The three-dimensional structure reveals the expected trimeric left-handed parallel beta-helix structure found in all other known hexapeptide repeat enzymes. In particular, the structure shows similarities both overall and at the putative active site to the recently determined structure of galactoside acetyltransferase (GAT), the lacA gene product [Wang, X.-G., Olsen, L. R., and Roderick, S. L. (2002) Structure 10, 581-588]. The structure, together with the new biochemical data, suggests that GAT and MAT are more closely related than previously thought and might have similar cellular functions. However, while GAT is specific for acetylation of galactosyl units, MAT is specific for glucosyl units and is able to acetylate maltooligosaccharides, an important property for biotechnological applications. Structural differences at the acceptor site reflect the differences in substrate specificity. 相似文献
43.
J Kaikkonen E Porkkala-Sarataho J D Morrow L J Roberts K Nyyss?nen R Salonen T P Tuomainen U Ristonmaa H E Poulsen J T Salonen 《Free radical research》2001,35(6):967-978
Although the use of vitamin E supplements has been associated with a reduction in coronary events, assumed to be due to lowered lipid peroxidation, there are no previous long-term clinical trials into the effects of vitamin C or E supplementation on lipid peroxidation in vivo. Here, we have studied the long-term effects of vitamins C and E on plasma F2-isoprostanes, a widely used marker of lipid peroxidation in vivo. As a study cohort, a subset of the "Antioxidant Supplementation in Atherosclerosis Prevention" (ASAP) study was used. ASAP is a double-masked placebo-controlled randomized clinical trial to study the long-term effect of vitamin C (500 mg of slow release ascorbate daily), vitamin E (200 mg of D-alpha-tocopheryl acetate daily), both vitamins (CellaVie), or placebo on lipid peroxidation, atherosclerotic progression, blood pressure and myocardial infarction (n = 520 at baseline). Lipid peroxidation measurements were carried out in 100 consecutive men at entry and repeated at 12 months. The plasma F2-isoprostane concentration was lowered by 17.3% (95% CI 3.9-30.8%) in the vitamin E group (p = 0.006 for the change, as compared with the placebo group). On the contrary, vitamin C had no significant effect on plasma F2-isoprostanes as compared with the placebo group. There was also no interaction in the effect between these vitamins. In conclusion, long-term oral supplementation of clinically healthy, but hypercholesterolemic men, who have normal vitamin C and E levels with a reasonable dose of vitamin E lowers lipid peroxidation in vivo, but a relatively high dose of vitamin C does not. This observation may provide a mechanism for the observed ability of vitamin E supplements to prevent atherosclerosis. 相似文献
44.
45.
46.
Vorup-Jensen T Petersen SV Hansen AG Poulsen K Schwaeble W Sim RB Reid KB Davis SJ Thiel S Jensenius JC 《Journal of immunology (Baltimore, Md. : 1950)》2000,165(4):2093-2100
Mannan-binding lectin (MBL) plays a pivotal role in innate immunity by activating complement after binding carbohydrate moieties on pathogenic bacteria and viruses. Structural similarities shared by MBL and C1 complexes and by the MBL- and C1q-associated serine proteases, MBL-associated serine protease (MASP)-1 and MASP-2, and C1r and C1s, respectively, have led to the expectation that the pathways of complement activation by MBL and C1 complexes are likely to be very similar. We have expressed rMASP-2 and show that, whereas C1 complex autoactivation proceeds via a two-step mechanism requiring proteolytic activation of both C1r and C1s, reconstitution with MASP-2 alone is sufficient for complement activation by MBL. The results suggest that the catalytic activities of MASP-2 split between the two proteases of the C1 complex during the course of vertebrate complement evolution. 相似文献
47.
A simple system for monitoring biodiversity in protected areas of a developing country 总被引:7,自引:3,他引:4
Finn Danielsen Danilo S. Balete Michael K. Poulsen Martin Enghoff Cristi M. Nozawa Arne E. Jensen 《Biodiversity and Conservation》2000,9(12):1671-1705
The achievements of initiatives to strengthen biodiversity conservation in developing countries may be difficult to assess, since most countries have no system for monitoring biodiversity. This paper describes a simple and cost-effective, field-based biodiversity monitoring system developed specifically for areas where specialist staff is lacking. We discuss the preliminary lessons learned from protected areas in the Philippines. Whilst the monitoring system aims to identify trends in biodiversity and its uses so as to guide management action, it also promotes the participation of local people in the management, stimulates discussions about conservation amongst stakeholders and builds the capacity of park staff and communities in management skills. In addition, it seeks to provide people with direction regarding the aims of protected areas, and reinforces the consolidation of existing livelihoods through strengthening community-based resource management systems. The field methods are: (1) standardised recording of routine observations, (2) fixed point photographing, (3) line transect survey, and (4) focus group discussion. Both bio-physical and socio-economic data are used and given equal importance. The system can be sustained using locally available resources. The approach is useful in countries embarking on shared management of park resources with local communities, where rural people depend on use of natural ecosystems, and where the economic resources for park management are limited. We hope this paper will encourage other countries to develop their own biodiversity monitoring system, letting its development become a means for capacity building whilst at the same time supporting the creation of ownership. 相似文献
48.
NMRsolution structures are reported for two mutants (K16E, K16F) of the soluble amyloid beta peptide Abeta(1-28). The structural effects of these mutations of a positively charged residue to anionic and hydrophobic residues at the alpha-secretase cleavage site (Lys16-Leu17) were examined in the membrane-simulating solvent aqueous SDS micelles. Overall the three-dimensional structures were similar to that for the native Abeta(1-28) sequence in that they contained an unstructured N-terminus and a helical C-terminus. These structural elements are similar to those seen in the corresponding regions of full-length Abeta peptides Abeta(1-40) and Abeta(1-42), showing that the shorter peptides are valid model systems. The K16E mutation, which might be expected to stabilize the macrodipole of the helix, slightly increased the helix length (residues 13-24) relative to the K16F mutation, which shortened the helix to between residues 16 and 24. The observed sequence-dependent control over conformation in this region provides an insight into possible conformational switching roles of mutations in the amyloid precursor protein from which Abeta peptides are derived. In addition, if conformational transitions from helix to random coil to sheet precede aggregation of Abeta peptides in vivo, as they do in vitro, the conformation-inducing effects of mutations at Lys16 may also influence aggregation and fibril formation. 相似文献
49.
Suh JK Poulsen LL Ziegler DM Robertus JD 《Archives of biochemistry and biophysics》2000,381(2):317-322
The flavin-dependent monooxygenase from yeast (yFMO) oxidizes biological thiols such as cysteine, cysteamine, and glutathione. The enzyme makes a major contribution to the pools of oxidized thiols that, together with reduced glutathione from glutathione reductase, create the optimum cellular redox environment. We show that the activity of yFMO, as a soluble enzyme or in association with the ER membrane of microsomal fractions, is correlated with the redox potential. The enzyme is active under conditions normally found in the cytoplasm, but is inhibited as GSSG accumulates to give a redox potential similar to that found in the lumen of the ER. Site-directed mutations show that Cys 353 and Cys 339 participate in the redox regulation. Cys 353 is the principal residue in the redox-sensitive switch. We hypothesize that it may initiate formation of a mixed disulfide that is partially inhibitory to yFMO. The mixed disulfide may exchange with Cys 339 to form an intramolecular disulfide bond that is fully inhibitory. 相似文献
50.
A burst phase in the early folding of the four-helix two-state folder protein acyl-coenzyme A binding protein (ACBP) has been detected using quenched-flow in combination with site-specific NMR-detected hydrogen exchange. Several of the burst phase structures coincide with a structure consisting of eight conserved hydrophobic residues at the interface between the two N and C-terminal helices. Previous mutation studies have shown that the formation of this structure is rate limiting for the final folding of ACBP. The burst phase structures observed in ACBP are different from the previously reported collapsed types of burst phase intermediates observed in the folding of other proteins. 相似文献