全文获取类型
收费全文 | 10609篇 |
免费 | 987篇 |
出版年
2022年 | 94篇 |
2021年 | 199篇 |
2020年 | 101篇 |
2019年 | 147篇 |
2018年 | 156篇 |
2017年 | 132篇 |
2016年 | 230篇 |
2015年 | 371篇 |
2014年 | 401篇 |
2013年 | 530篇 |
2012年 | 684篇 |
2011年 | 617篇 |
2010年 | 417篇 |
2009年 | 344篇 |
2008年 | 507篇 |
2007年 | 496篇 |
2006年 | 494篇 |
2005年 | 431篇 |
2004年 | 485篇 |
2003年 | 435篇 |
2002年 | 424篇 |
2001年 | 215篇 |
2000年 | 202篇 |
1999年 | 175篇 |
1998年 | 119篇 |
1997年 | 100篇 |
1996年 | 122篇 |
1995年 | 80篇 |
1994年 | 95篇 |
1993年 | 102篇 |
1992年 | 114篇 |
1991年 | 136篇 |
1990年 | 130篇 |
1989年 | 93篇 |
1988年 | 117篇 |
1987年 | 120篇 |
1986年 | 114篇 |
1985年 | 111篇 |
1984年 | 85篇 |
1983年 | 68篇 |
1982年 | 87篇 |
1981年 | 80篇 |
1980年 | 62篇 |
1979年 | 75篇 |
1978年 | 76篇 |
1977年 | 61篇 |
1976年 | 54篇 |
1975年 | 60篇 |
1973年 | 66篇 |
1972年 | 50篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Combining substrate dynamics, binding statistics, and energy barriers to rationalize regioselective hydroxylation of octane and lauric acid by CYP102A1 and mutants
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)
Feenstra KA Starikov EB Urlacher VB Commandeur JN Vermeulen NP 《Protein science : a publication of the Protein Society》2007,16(3):420-431
Hydroxylations of octane and lauric acid by Cytochrome P450-BM3 (CYP102A1) wild-type and three active site mutants--F87A, L188Q/A74G, and F87V/L188Q/A74G--were rationalized using a combination of substrate orientation from docking, substrate binding statistics from molecular dynamics simulations, and barrier energies for hydrogen atom abstraction from quantum mechanical calculations. Wild-type BM3 typically hydroxylates medium- to long-chain fatty acids on subterminal (omega-1, omega-2, omega-3) but not the terminal (omega) positions. The known carboxylic anchoring site Y51/R47 for lauric acid, and hydrophobic interactions and steric exclusion, mainly by F87, for octane as well as lauric acid, play a role in the binding modes of the substrates. Electrostatic interactions between the protein and the substrate strongly modulate the substrate's regiodependent activation barriers. A combination of the binding statistics and the activation barriers of hydrogen-atom abstraction in the substrates is proposed to determine the product formation. Trends observed in experimental product formation for octane and lauric acid by wild-type BM3 and the three active site mutants were qualitatively explained. It is concluded that the combination of substrate binding statistics and hydrogen-atom abstraction barrier energies is a valuable tool to rationalize substrate binding and product formation and constitutes an important step toward prediction of product ratios. 相似文献
992.
The translocated intimin receptor (TIR) of enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC) is required for EPEC and EHEC infections, which cause widespread illness across the globe. TIR is translocated via a type-III secretion system into the intestinal epithelial cell membrane, where it serves as an anchor for E. coli attachment via its binding partner intimin. While many aspects of EPEC and EHEC infection are now well understood, the importance of the intermolecular contacts made between intimin and TIR have not been thoroughly investigated. Herein we report site-directed mutagenesis studies on the intimin-binding domain of EPEC TIR, and how these mutations affect TIR-intimin association, as analyzed by isothermal titration calorimetry and circular dichroism. These results show how two factors govern TIR's binding to intimin: A three-residue TIR hot spot is identified that largely mediates the interaction, and mutants that alter the beta-hairpin structure of TIR severely diminish binding affinity. In addition, peptides incorporating key TIR residues identified by mutagenesis are incapable of binding intimin. These results indicate that hot spot residues and structural orientation/preorganization are required for EPEC, and likely EHEC, TIR-intimin binding. 相似文献
993.
Abandoning aggression but maintaining self-nonself discrimination as a first stage in ant supercolony formation 总被引:2,自引:0,他引:2
Steiner FM Schlick-Steiner BC Moder K Stauffer C Arthofer W Buschinger A Espadaler X Christian E Einfinger K Lorbeer E Schafellner C Ayasse M Crozier RH 《Current biology : CB》2007,17(21):1903-1907
An ant supercolony is a very large entity with very many queens. Although normal colonies of small extent and few queens remain distinct, a supercolony is integrated harmoniously over a large area [1, 2]. The lack of aggression is advantageous: Aggression is costly, involving direct and indirect losses and recognition errors [3, 4]. Indeed, supercolonial ants are among the ecologically most successful organisms [5-7]. But how supercolonies arise remains mysterious [1, 2, 8]. Suggestions include that reduced within-colony relatedness or reduced self-nonself discrimination would foster supercolony formation [1, 2, 5, 7, 9-12]. However, one risks confusing correlation and causality in deducing the evolution from distinct colonies to supercolonies when observing established supercolonies. It might help to follow up observations of another lack of aggression, that between single-queened colonies in some ant species. We show that the single-queened Lasius austriacus lacks aggression between colonies and occasionally integrates workers across colonies but maintains high within-colony relatedness and self-nonself discrimination. Provided that the ecological framework permits, reduced aggression might prove adaptive for any ant colony irrespective of within-colony relatedness. Abandoning aggression while maintaining discrimination might be a first stage in supercolony formation. This adds to the emphasis of ecology as central to the evolution of cooperation in general [13]. 相似文献
994.
The synthesis and biological evaluation of a new class of selective irreversible cysteine protease inhibitors is described. A set of amino acid based chloromethyl sulfoxides was prepared and they were found to inhibit irreversibly the cysteine protease papain. They were selective for cysteine proteases since no inhibition was found for the serine protease chymotrypsin. 相似文献
995.
Muraski JA Rota M Misao Y Fransioli J Cottage C Gude N Esposito G Delucchi F Arcarese M Alvarez R Siddiqi S Emmanuel GN Wu W Fischer K Martindale JJ Glembotski CC Leri A Kajstura J Magnuson N Berns A Beretta RM Houser SR Schaefer EM Anversa P Sussman MA 《Nature medicine》2007,13(12):1467-1475
The serine-threonine kinases Pim-1 and Akt regulate cellular proliferation and survival. Although Akt is known to be a crucial signaling protein in the myocardium, the role of Pim-1 has been overlooked. Pim-1 expression in the myocardium of mice decreased during postnatal development, re-emerged after acute pathological injury in mice and was increased in failing hearts of both mice and humans. Cardioprotective stimuli associated with Akt activation induced Pim-1 expression, but compensatory increases in Akt abundance and phosphorylation after pathological injury by infarction or pressure overload did not protect the myocardium in Pim-1-deficient mice. Transgenic expression of Pim-1 in the myocardium protected mice from infarction injury, and Pim-1 expression inhibited cardiomyocyte apoptosis with concomitant increases in Bcl-2 and Bcl-X(L) protein levels, as well as in Bad phosphorylation levels. Relative to nontransgenic controls, calcium dynamics were significantly enhanced in Pim-1-overexpressing transgenic hearts, associated with increased expression of SERCA2a, and were depressed in Pim-1-deficient hearts. Collectively, these data suggest that Pim-1 is a crucial facet of cardioprotection downstream of Akt. 相似文献
996.
997.
998.
Fischer GA Gravendeel B Sieder A Andriantiana J Heiselmayer P Cribb PJ Smidt Ede C Samuel R Kiehn M 《Molecular phylogenetics and evolution》2007,45(1):358-376
Resupination is the orientation of zygomorphic flowers during development so that the median petal obtains the lowermost position in the mature flower. Despite its evolutionary and ecological significance, resupination has rarely been studied in a phylogenetic context. Ten types of resupination occur among the 210 species of the orchid genus Bulbophyllum on Madagascar. We investigated the evolution of resupination in a representative sample of these species by first reconstructing a combined nrITS and cpDNA phylogeny for a sectional reclassification and then plotting the different types of inflorescence development, which correlated well with main clades. Resupination by apical drooping of the rachis appears to have evolved from apical drooping of the peduncle. Erect inflorescences with resupinate flowers seem to have evolved several times into either erect inflorescences with (partly) non-resupinate flowers or pendulous inflorescences with resupinate flowers. 相似文献
999.
DNA sequences from three mitochondrial (rrnL, cox2, nad2) and one nuclear gene (itpr) from all 9 known honey bee species (Apis), a 10th possible species, Apis dorsata binghami, and three outgroup species (Bombus terrestris, Melipona bicolor and Trigona fimbriata) were used to infer Apis phylogenetic relationships using Bayesian analysis. The dwarf honey bees were confirmed as basal, and the giant and cavity-nesting species to be monophyletic. All nodes were strongly supported except that grouping Apis cerana with A. nigrocincta. Two thousand post-burnin trees from the phylogenetic analysis were used in a Bayesian comparative analysis to explore the evolution of dance type, nest structure, comb structure and dance sound within Apis. The ancestral honey bee species was inferred with high support to have nested in the open, and to have more likely than not had a silent vertical waggle dance and a single comb. The common ancestor of the giant and cavity-dwelling bees is strongly inferred to have had a buzzing vertical directional dance. All pairwise combinations of characters showed strong association, but the multiple comparisons problem reduces the ability to infer associations between states between characters. Nevertheless, a buzzing dance is significantly associated with cavity-nesting, several vertical combs, and dancing vertically, a horizontal dance is significantly associated with a nest with a single comb wrapped around the support, and open nesting with a single pendant comb and a silent waggle dance. 相似文献
1000.
New photoreactive tRNA derivatives for probing the peptidyl transferase center of the ribosome
下载免费PDF全文
![点击此处可从《RNA (New York, N.Y.)》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Three new photoreactive tRNA derivatives have been synthesized for use as probes of the peptidyl transferase center of the ribosome. In two of these derivatives, the 3' adenosine of yeast tRNA(Phe) has been replaced by either 2-azidodeoxyadenosine or 2-azido-2'-O-methyl adenosine, while in a third the 3'-terminal 2-azidodeoxyadenosine of the tRNA is joined to puromycin via a phosphoramidate linkage to generate a photoreactive transition-state analog. All three derivatives bind to the P site of 70S ribosomes with affinities similar to that of unmodified tRNA(Phe) and can be cross-linked to components of the 50S ribosomal subunit by irradiation with near-UV light. Characteristic differences in the cross-linking patterns suggest that these tRNA derivatives can be used to follow subtle changes in the position of the tRNA relative to the components of the peptidyl transferase center. 相似文献