全文获取类型
收费全文 | 6946篇 |
免费 | 687篇 |
国内免费 | 1184篇 |
出版年
2024年 | 18篇 |
2023年 | 190篇 |
2022年 | 201篇 |
2021年 | 283篇 |
2020年 | 350篇 |
2019年 | 395篇 |
2018年 | 304篇 |
2017年 | 274篇 |
2016年 | 236篇 |
2015年 | 283篇 |
2014年 | 329篇 |
2013年 | 518篇 |
2012年 | 232篇 |
2011年 | 327篇 |
2010年 | 297篇 |
2009年 | 333篇 |
2008年 | 365篇 |
2007年 | 344篇 |
2006年 | 362篇 |
2005年 | 342篇 |
2004年 | 264篇 |
2003年 | 275篇 |
2002年 | 242篇 |
2001年 | 152篇 |
2000年 | 128篇 |
1999年 | 131篇 |
1998年 | 141篇 |
1997年 | 109篇 |
1996年 | 112篇 |
1995年 | 120篇 |
1994年 | 107篇 |
1993年 | 89篇 |
1992年 | 101篇 |
1991年 | 73篇 |
1990年 | 86篇 |
1989年 | 64篇 |
1988年 | 74篇 |
1987年 | 58篇 |
1986年 | 52篇 |
1985年 | 56篇 |
1984年 | 75篇 |
1983年 | 43篇 |
1982年 | 56篇 |
1981年 | 60篇 |
1980年 | 42篇 |
1979年 | 40篇 |
1978年 | 18篇 |
1977年 | 16篇 |
1976年 | 19篇 |
1974年 | 9篇 |
排序方式: 共有8817条查询结果,搜索用时 15 毫秒
991.
Wang RX 《Journal of evolutionary biology》2003,16(2):353-361
Abstract In animals, if one sex of the F1 hybrid between two species is sterile or inviable, it is usually the heterogametic (XY or WZ) sex. This phenomenon, known as Haldane's rule, is currently thought to be coincidentally caused by different mechanisms in separate entities. The following questions have never been asked: Are heterogametic and homogametic inferiority (sterility or inviability) equivalent as isolating mechanisms? Could discrepancies between them, if existing, produce Haldane's rule? Here I consider sex‐biased hybrid inferiority strictly as an isolating mechanism, and quantitatively evaluate its strength in impeding gene flow. The comparison reveals that the ability of sex‐biased inferiority to impede gene flow varies according to the sex and chromosome involved. Heterogametic inferiority is a weaker barrier when unidirectional and a much stronger one when in compound reciprocal directions, compared with homogametic inferiority. Such differential strength may affect divergence in speciation and produce Haldane's rule. 相似文献
992.
O. O. Burdelev A. P. Kaplun L. V. Kozlov S. V. Lysakova V. L. D'yakov V. I. Shvets 《Russian Journal of Bioorganic Chemistry》2003,29(2):139-142
Polyethyleneimine (PEI, 50 kDa) and polymethacrylic acid (PMA, 200 kDa) were shown to inhibit the lysis of sheep erythrocytes induced by the guinea pig complement. They twofold suppress the hemolysis at the concentrations of 0.47 and 0.89 g/ml, respectively. The inhibitory effect on the binding of the C1q subunit of human complement to the sensitized sheep erythrocytes (EA) was found to depend on the component of the reaction with which the inhibitors were preliminarily incubated. When an inhibitor, C1q, and EA were simultaneously incubated, the inhibition constants for PEI and PMA were 17 ± 6 and 8.1 ± 0.1 g/ml, respectively. The preincubation of EA with PEI and the subsequent washing out of the inhibitor resulted in the inhibition constant of 22 ± 3 g/ml. No inhibitory effect was observed after a similar preincubation of EA with PMA. No inhibition was also detected when the inhibitors were added after the formation of the C1q complex with antibodies. These observations suggest that the binding of antibodies to cationic PEI prevents the C1q–antibody complex formation, while the binding of anionic PMA to the active site of C1q impedes the interaction of this subunit with immunoglobulins. Moreover, within the range of concentrations studied, the studied inhibitors did not affect the subsequent C1q binding to the C1r and C1s enzymes. 相似文献
993.
Paulina Juszczyk Regina Kasprzykowska Aleksandra S. Koodziejczyk 《Letters in Peptide Science》2003,10(2):79-82
Sodium bis(2-methoxyethoxy)aluminum hydride, NaAlH2(OCH2CH2OCH3)2, commercially known as Vitride® or Red-Al®, enables rapid synthesis of pure optically active N-protected amino alcohols and peptide alcohols in very high yields. The method is very simple and attractive, as it does not require an additional step of N-protected amino acid derivatization and proceeds without the loss of enantiomeric homogeneity. 相似文献
994.
Osborne MJ Venkitakrishnan RP Dyson HJ Wright PE 《Protein science : a publication of the Protein Society》2003,12(10):2230-2238
Heteronuclear NMR methods have been used to probe the conformation of four complexes of Escherichia coli dihydrofolate reductase (DHFR) in solution. (1)H(N), (15)N, and (13)C(alpha) resonance assignments have been made for the ternary complex with folate and oxidized NADP(+) cofactor and the ternary complex with folate and a reduced cofactor analog, 5,6-dihydroNADPH. The backbone chemical shifts have been compared with those of the binary complex of DHFR with the substrate analog folate and the binary complex with NADPH (the holoenzyme). Analysis of (1)H(N) and (15)N chemical shifts has led to the identification of marker resonances that report on the active site conformation of the enzyme. Other backbone amide resonances report on the presence of ligands in the pterin binding pocket and in the adenosine and nicotinamide-ribose binding sites of the NADPH cofactor. The chemical shift data indicate that the enzyme populates two dominant structural states in solution, with the active site loops in either the closed or occluded conformations defined by X-ray crystallography; there is no evidence that the open conformation observed in some X-ray structures of E. coli DHFR are populated in solution. 相似文献
995.
Farnum MA Xu H Agrafiotis DK 《Protein science : a publication of the Protein Society》2003,12(8):1604-1612
The explosion of biological data resulting from genomic and proteomic research has created a pressing need for data analysis techniques that work effectively on a large scale. An area of particular interest is the organization and visualization of large families of protein sequences. An increasingly popular approach is to embed the sequences into a low-dimensional Euclidean space in a way that preserves some predefined measure of sequence similarity. This method has been shown to produce maps that exhibit global order and continuity and reveal important evolutionary, structural, and functional relationships between the embedded proteins. However, protein sequences are related by evolutionary pathways that exhibit highly nonlinear geometry, which is invisible to classical embedding procedures such as multidimensional scaling (MDS) and nonlinear mapping (NLM). Here, we describe the use of stochastic proximity embedding (SPE) for producing Euclidean maps that preserve the intrinsic dimensionality and metric structure of the data. SPE extends previous approaches in two important ways: (1) It preserves only local relationships between closely related sequences, thus allowing the map to unfold and reveal its intrinsic dimension, and (2) it scales linearly with the number of sequences and therefore can be applied to very large protein families. The merits of the algorithm are illustrated using examples from the protein kinase and nuclear hormone receptor superfamilies. 相似文献
996.
997.
Liu D Windsor WT Wyss DF 《Protein science : a publication of the Protein Society》2003,12(12):2757-2767
The NS3 helicase of the hepatitis C virus (HCV) unwinds double-stranded (ds) nucleic acid (NA) in an NTP-dependent fashion. Mechanistic details of this process are, however, largely unknown for the HCV helicase. We have studied the binding of dsDNA to an engineered version of subdomain 2 of the HCV helicase (d(2Delta)NS3h) by NMR and circular dichroism. Binding of dsDNA to d(2Delta)NS3h induces a local unfolding of helix (alpha(3)), which includes residues of conserved helicase motif VI (Q(460)RxxRxxR(467)), and strands (beta(1) and beta(8)) from the central beta-sheet. This also occurs upon lowering the pH (4.4) and introducing an R461A point mutation, which disrupt salt bridges with Asp 412 and Asp 427 in the protein structure. NMR studies on d(2Delta)NS3h in the partially unfolded state at low pH map the dsDNA binding site to residues previously shown to be involved in single-stranded DNA binding. Sequence alignment and structural comparison suggest that these Arg-Asp interactions are highly conserved in SF2 DEx(D/H) proteins. Thus, modulation of these interactions by dsNA may allow SF2 helicases to switch between conformations required for helicase function. 相似文献
998.
The processes by which protein side chains reach equilibrium during a folding reaction are investigated using both lattice and all-atom simulations. We find that rates of side-chain relaxation exhibit a distribution over the protein structure, with the fastest relaxing side chains located in positions kinetically important for folding. Traversal of the major folding transition state corresponds to the freezing of a small number of side chains, belonging to the folding nucleus, whereas the rest of the protein proceeds toward equilibrium via backbone fluctuations around the native fold. The postnucleation processes by which side chains relax are characterized by very slow dynamics and many barrier crossings, and thus resemble the behavior of a glass. 相似文献
999.
Koumanov A Benach J Atrian S Gonzàlez-Duarte R Karshikoff A Ladenstein R 《Proteins》2003,51(2):289-298
The ionization properties of the active site residues in Drosophila lebanonensis alcohol dehydrogenase (DADH) were investigated theoretically by using an approach developed to account for multiple locations of the hydrogen atoms of the titratable and polar groups. The electrostatic calculations show that (a) the protonation/deprotonation transition of the binary complex of DADH is related to the coupled ionization of Tyr151 and Lys155 in the active site and (b) the pH dependence of the proton abstraction is correlated with a reorganization of the hydrogen bond network in the active site. On this basis, a proton relay mechanism for substrate dehydrogenation is proposed in which the O2' ribose hydroxyl group from the coenzyme has a key role and acts as a switch. The proton relay chain includes the active site catalytic residues, as well as a chain of eight water molecules that connects the active site with the bulk solvent. 相似文献
1000.
A high-affinity ligand for the type II estrogen binding site (EBS) was identified. Methyl para-hydroxyphenyllactate (MeHPLA) was observed to suppress the cellular proliferation of estrogen-sensitive MCF-7 breast cancer cells in vitro and to suppress the growth of rat uteri in vivo. The high affinity of MeHPLA for the type II EBS suggests that this interaction is responsible for the observed suppression of cell growth. In this study, the enantiomers of MeHPLA were synthesized and separated by three methods and evaluated for biological activity. When the methods were compared, it was found that the method using an optically pure amine to form the diastereomers of the enantiomers gave the superior yield. Binding studies for the enantiomers to the type II EBS showed that the S-MeHPLA had a higher affinity for the binding site. However, higher binding affinity did not translate into superior cell growth suppression. Both enantiomers suppressed cell growth equally. 相似文献