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121.
M. Teresa García-López Ibon Alkorta M. José Domínguez Rosario González-Mu?iz Rosario Herranz Nils L. Johansen Kjeld Madsen Henning Th?gersen Peter Suzdak 《Letters in Peptide Science》1995,1(6):269-276
Summary In order to enforce different spatial orientations in the C-terminal hexapeptide of neurotensin (NT8–13) and to gain information about the importance of the 10–11 peptide bond for binding to NT receptors, the Pro10-Tyr11 fragment has been replaced with (2R,8S,8aR)-, (2S,8S,8aR)-, (2S,8S,8aS)-, (2S,8R,8aS)- and (2R,8R,8aS)-8-amino-2-benzyl-3-oxoindolizidine-2-carboxylic acid. Molecular dynamics calculations and energy minimization studies have shown that, contrarily to the Pro-Tyr moiety, none of these indolizidines display a tendency to adopt type I and III -turns, but those having (8S,8aR) or (8R,8aS) stereochemistry essentially adopt extended conformations and the (8S,8aS) stereoisomer prefers a nonstandard folding. The four diastereomeric NT8–13 analogues incorporating (8S,8aR) or (8R,8aS) indolizidines displayed binding affinities for the brain NT receptor similar to that of [Ala11]-NT8–13 and only five- to ninefold lower than that of the corresponding analogue, [Phe11]NT8–13. Although this slight decrease could be attributed to differences in conformational behavior between these constrained NT8–13 analogues and [Phe11]NT8–13 or NT8–13, it is not clear whether the -turn around Pro10-AA11 (AA=Phe, Tyr) is conserved upon receptor binding. An excessive restriction in the motions of the aromatic side chain, imposed by the highly steric constraint of the indolizidine moiety, emerges as an alternative explanation. The findings reported here demonstrate the possibility of replacing the Pro10-Tyr11 dipeptide in NT8–13 with a non-peptide residue without affecting considerably the affinity for brain NT receptors. 相似文献
122.
Various nonlinear regenerative responses, including plateau potentials and bistable repetitive firing modes, have been observed in motoneurons under certain conditions. Our simulation results support the hypothesis that these responses are due to plateau-generating currents in the dendrites, consistent with a major role for a noninactivating calcium L-type current as suggested by experiments. Bistability as observed in the soma of low- and higher-frequency spiking or, under TTX, of near resting and depolarized plateau potentials, occurs because the dendrites can be in a near resting or depolarized stable steady state. We formulate and study a two-compartment minimal model of a motoneuron that segregates currents for fast spiking into a soma-like compartment and currents responsible for plateau potentials into a dendrite-like compartment. Current flows between compartments through a coupling conductance, mimicking electrotonic spread. We use bifurcation techniques to illuminate how the coupling strength affects somatic behavior. We look closely at the case of weak coupling strength to gain insight into the development of bistable patterns. Robust somatic bistability depends on the electrical separation since it occurs only for weak to moderate coupling conductance. We also illustrate that hysteresis of the two spiking states is a natural consequence of the plateau behavior in the dendrite compartment. 相似文献
123.
Building proteins from C alpha coordinates using the dihedral probability grid Monte Carlo method. 总被引:2,自引:2,他引:0 下载免费PDF全文
A. M. Mathiowetz W. A. Goddard rd 《Protein science : a publication of the Protein Society》1995,4(6):1217-1232
Dihedral probability grid Monte Carlo (DPG-MC) is a general-purpose method of conformational sampling that can be applied to many problems in peptide and protein modeling. Here we present the DPG-MC method and apply it to predicting complete protein structures from C alpha coordinates. This is useful in such endeavors as homology modeling, protein structure prediction from lattice simulations, or fitting protein structures to X-ray crystallographic data. It also serves as an example of how DPG-MC can be applied to systems with geometric constraints. The conformational propensities for individual residues are used to guide conformational searches as the protein is built from the amino-terminus to the carboxyl-terminus. Results for a number of proteins show that both the backbone and side chain can be accurately modeled using DPG-MC. Backbone atoms are generally predicted with RMS errors of about 0.5 A (compared to X-ray crystal structure coordinates) and all atoms are predicted to an RMS error of 1.7 A or better. 相似文献
124.
Molecular model of the N-terminal receptor-binding domain of the human CD6 ligand ALCAM. 总被引:2,自引:1,他引:1 下载免费PDF全文
J. Bajorath M. A. Bowen A. Aruffo 《Protein science : a publication of the Protein Society》1995,4(8):1644-1647
CD6-ligand interactions have been implicated in the regulation of T-cell adhesion and activation. CD6 is a member of the scavenger receptor family, whereas its human ligand (ALCAM) belongs to the immunoglobulin superfamily. The extracellular region of ALCAM includes five immunoglobulin-like domains. As a fusion protein, the N-terminal extracellular domain of ALCAM (ALCAMD1) binds specifically to CD6. We report the construction, assessment, and analysis of a molecular model of ALCAMD1. The model defines the CDR-analogous loops, the location of N-linked glycosylation sites, and residues that form the beta-sheet faces of the immunoglobulin-like domain. Predicted structural characteristics of the A'GFCC'C" face of the model are consistent with the presence of monomeric and dimeric forms of ALCAMD1, which has implications for the receptor-ligand interactions. 相似文献
125.
Frank D. Snnichsen Brian D. Sykes Peter L. Davies 《Protein science : a publication of the Protein Society》1995,4(3):460-471
Type II antifreeze proteins (AFP), which inhibit the growth of seed ice crystals in the blood of certain fishes (sea raven, herring, and smelt), are the largest known fish AFPs and the only class for which detailed structural information is not yet available. However, a sequence homology has been recognized between these proteins and the carbohydrate recognition domain of C-type lectins. The structure of this domain from rat mannose-binding protein (MBP-A) has been solved by X-ray crystallography (Weis WI, Drickamer K, Hendrickson WA, 1992, Nature 360:127-134) and provided the coordinates for constructing the three-dimensional model of the 129-amino acid Type II AFP from sea raven, to which it shows 19% sequence identity. Multiple sequence alignments between Type II AFPs, pancreatic stone protein, MBP-A, and as many as 50 carbohydrate-recognition domain sequences from various lectins were performed to determine reliably aligned sequence regions. Successive molecular dynamics and energy minimization calculations were used to relax bond lengths and angles and to identify flexible regions. The derived structure contains two alpha-helices, two beta-sheets, and a high proportion of amino acids in loops and turns. The model is in good agreement with preliminary NMR spectroscopic analyses. It explains the observed differences in calcium binding between sea raven Type II AFP and MBP-A. Furthermore, the model proposes the formation of five disulfide bridges between Cys 7 and Cys 18, Cys 35 and Cys 125, Cys 69 and Cys 100, Cys 89 and Cys 111, and Cys 101 and Cys 117.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
126.
蒲洼农业生态系统能流的稳定性及其动态 总被引:1,自引:0,他引:1
在研究生态系统结构及功能的基础上,本文基于1975-1990年的数据,对蒲洼农业生态系统能流的稳定性及其动态进行了分析。通过建立能流模型,由李雅普诺夫稳定性原理,得出该生态系统能流的平衡态具有渐近稳定性。动态数学模拟表明,目前该系统的能量流动正从不稳定状态向稳定和平衡态过渡,这一过程大约需要7a时间。 相似文献
127.
128.
Undesirable aggregation of aqueous insulin solutions remains a serious obstacle in the development of alternative methods of diabetes therapy. We investigated the fundamental nature of the aggregation mechanism and proposed stabilization strategies based on a mathematical model for the reaction scheme. Insulin aggregation kinetics in the presence of solid-liquid and air-liquid interfaces were monitored using UV spectroscopy and quasielastic light scattering (QELS). Experimental observations were consistent with our model of monomer denaturation at hydrophobic surfaces followed by the formation of stable intermediate species which facilitated subsequent macroaggregation. The model was used to predict qualitative trends in insulin aggregation behavior, to propose stabilization strategies, and to elucidate mechanisms of stabilization. In the absence of additives, insulin solutions aggregated completely (more than 95% of the soluble protein lost) within 24 h; with sugarbased nonionic detergents, no detectable loss occurred for more than 6 weeks. (c) 1992 John Wiley & Sons, Inc. 相似文献
129.
Modeling high-biomass-density cell recycle fermentors 总被引:1,自引:0,他引:1
Monbouquette HG 《Biotechnology and bioengineering》1992,39(5):498-503
Since intrinsic models, which take into account cell volume fraction, follow from proper application of the law of conservation of mass to a multiphase system, the intrinsic modeling approach should be used whenever biomass occupies a significant volume fraction of the culture. A recent report(11) offers the first comparison of intrinsic and nonintrinsic model predictions to actual experimental data gathered from a high-density yeast recycle fermentor. Here, the analysis of Jarzebski et al.(11) has been carried further to show that the improper nonintrinsic model predicts a steady-state culture glucose concentration that differs from that given by the fundamentally correct intrinsic model by over 60% at the optimal, bleed stream flow rate. In addition, a revised formulation for an intrinsic ethanol mass balance is presented. 相似文献
130.
There is strong evidence in the literature supporting the existence of significant mass transfer limitations on the kinetics of exogenous H(2) consumption by methanogens. The half saturation constant for H (2) uptake by a mixed-culture, CH(4) producing enrichment was measured using an experimental protocol that avoided internal mass transfer limitations. The value obtained was two orders of magnitude smaller than any other previously reported. A mathematical model for acetogenic syntrophic associations was developed to check the capacity of H(2) as electron transporter between syntrophic partners. It was found that H(2) diffusion could account for the rate of transport of electrons between the syntrophic microorganisms and that formate is not a necessary intermediate. The possibility that formate may be an intermediate in this system was not ruled out. A Monod-type kinetic equation was modified to include the observed H(2) threshold effect. This modified equation was used to predict the CH(4)-production rate in a batch-fed digester. The results show that the external and internal H(2) pools are kinetically coupled. (c) 1992 John Wiley & Sons, Inc. 相似文献