全文获取类型
收费全文 | 1286篇 |
免费 | 152篇 |
国内免费 | 6篇 |
出版年
2024年 | 5篇 |
2023年 | 25篇 |
2022年 | 31篇 |
2021年 | 47篇 |
2020年 | 75篇 |
2019年 | 88篇 |
2018年 | 98篇 |
2017年 | 72篇 |
2016年 | 70篇 |
2015年 | 57篇 |
2014年 | 80篇 |
2013年 | 191篇 |
2012年 | 40篇 |
2011年 | 67篇 |
2010年 | 43篇 |
2009年 | 53篇 |
2008年 | 52篇 |
2007年 | 46篇 |
2006年 | 44篇 |
2005年 | 40篇 |
2004年 | 37篇 |
2003年 | 27篇 |
2002年 | 28篇 |
2001年 | 15篇 |
2000年 | 18篇 |
1999年 | 18篇 |
1998年 | 14篇 |
1997年 | 11篇 |
1996年 | 11篇 |
1995年 | 6篇 |
1994年 | 8篇 |
1993年 | 12篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1979年 | 1篇 |
1978年 | 1篇 |
排序方式: 共有1444条查询结果,搜索用时 31 毫秒
101.
Phylogenetic studies based on DNA sequences typically ignore the potential occurrence of recombination, which may produce different alignment regions with different evolutionary histories. Traditional phylogenetic methods assume that a single history underlies the data. If recombination is present, can we expect the inferred phylogeny to represent any of the underlying evolutionary histories? We examined this question by applying traditional phylogenetic reconstruction methods to simulated recombinant sequence alignments. The effect of recombination on phylogeny estimation depended on the relatedness of the sequences involved in the recombinational event and on the extent of the different regions with different phylogenetic histories. Given the topologies examined here, when the recombinational event was ancient, or when recombination occurred between closely related taxa, one of the two phylogenies underlying the data was generally inferred. In this scenario, the evolutionary history corresponding to the majority of the positions in the alignment was generally recovered. Very different results were obtained when recombination occurred recently among divergent taxa. In this case, when the recombinational breakpoint divided the alignment in two regions of similar length, a phylogeny that was different from any of the true phylogenies underlying the data was inferred. 相似文献
102.
Fernández A 《Proteins》2002,47(4):447-457
A method is presented to identify hot mutational spots and predict the extent of surface burial at the transition state relative to the native fold in two-state folding proteins. The method is based on ab initio simulations of folding histories in which transitions between coarsely defined conformations and pairwise interactions are dependent on the solvent environments created by the chain. The highly conserved mammalian ubiquitin is adopted as a study case to make predictions. The evolution in time of the chain topology suggests a nucleation process with a critical point signaled by a sudden quenching of structural fluctuations. The occurrence of this nucleus is shown to be concurrent with a sudden escalation in the number of three-body correlations whereby hydrophobic units approach residue pairs engaged in amide-carbonyl hydrogen bonding. These correlations determine a pattern designed to structure the surrounding solvent, protecting intramolecular hydrogen bonds from water attack. Such correlations are shown to be required to stabilize the nucleus, with kinetic consequences for the folding process. Those nuclear residues that adopt the dual role of protecting and being protected while engaged in hydrogen bonds are predicted to be the hottest mutational spots. Some such residues are shown not to retain the same protecting role in the native fold. This kinetic treatment of folding nucleation is independently validated vis-a-vis a Phi-value analysis on chymotrypsin inhibitor 2, a protein for which extensive mutational data exists. 相似文献
103.
Monte Carlo simulations of molecular recognition at the consensus binding site of the constant fragment (Fc) of human immunoglobulin G (Ig) protein have been performed to analyze structural and thermodynamic aspects of binding for the 13-residue cyclic peptide DCAWHLGELVWCT. The energy landscape analysis of a hot spot at the intermolecular interface using alanine scanning and equilibrium-simulated tempering dynamics with the simplified, knowledge-based energy function has enabled the role of the protein hot spot residues in providing the thermodynamic stability of the native structure to be determined. We have found that hydrophobic interactions between the peptide and the Met-252, Ile-253, His-433, and His-435 protein residues are critical to guarantee the thermodynamic stability of the crystallographic binding mode of the complex. Binding free energy calculations, using a molecular mechanics force field and a solvation energy model, combined with alanine scanning have been conducted to determine the energetic contribution of the protein hot spot residues in binding affinity. The conserved Asn-434, Ser-254, and Tyr-436 protein residues contribute significantly to the binding affinity of the peptide-protein complex, serving as an energetic hot spot at the intermolecular interface. The results suggest that evolutionary conserved hot spot protein residues at the intermolecular interface may be partitioned in fulfilling thermodynamic stability of the native binding mode and contributing to the binding affinity of the complex. 相似文献
104.
Lazaridis T 《Proteins》2003,52(2):176-192
A simple extension of the EEF1 energy function to heterogeneous membrane-aqueous media is proposed. The extension consists of (a) development of solvation parameters for a nonpolar phase using experimental data for the transfer of amino acid side-chains from water to cyclohexane, (b) introduction of a heterogeneous membrane-aqueous system by making the reference solvation free energy of each atom dependent on the vertical coordinate, (c) a modification of the distance-dependent dielectric model to account for reduced screening of electrostatic interactions in the membrane, and (d) an adjustment of the EEF1 aqueous model in light of recent calculations of the potential of mean force between amino acid side-chains in water. The electrostatic model is adjusted to match experimental observations for polyalanine, polyleucine, and the glycophorin A dimer. The resulting energy function (IMM1) reproduces the preference of Trp and Tyr for the membrane interface, gives reasonable energies of insertion into or adsorption onto a membrane, and allows stable 1-ns MD simulations of the glycophorin A dimer. We find that the lowest-energy orientation of melittin in bilayers varies, depending on the thickness of the hydrocarbon layer. 相似文献
105.
Oscillations in the electrostatic energy gap [Velec(t)] for electron transfer from the primary electron donor (P) to the adjacent bacteriochlorophyll (B) in photosynthetic bacterial reaction centers are examined by molecular-dynamics simulations. Autocorrelation functions of Velec in the reactant state (PB) include prominent oscillations with an energy of 17 cm–1. This feature is much weaker if the trajectory is propagated in the product state P+B–. The autocorrelation functions also include oscillations in the regions of 5, 80 and 390 cm–1 in both states, and near 25 and 48 cm–1 in P+B–. The strong 17-cm–1 oscillation could involve motions that modulate the distance between P and B, because a similar oscillation occurs in the direct electrostatic interactions between the electron carriers. 相似文献
106.
Timothy D. O'Hara 《Global Ecology and Biogeography》2007,16(6):720-732
Aim To test the hypotheses that seamounts exhibit high rates of endemism and/or species richness compared to surrounding areas of the continental slope and oceanic ridges. Location The south‐west Pacific Ocean from 19–57° S to 143–171° E. Methods Presence/absence museum data were compiled for seamount and non‐seamount areas at depths between 100 and 1500 m for the Ophiuroidea (brittle‐stars), an abundant and speciose group of benthic invertebrates. Large‐scale biogeographical gradients were examined through multivariate analyses at two spatial scales, at the scale of seamounts (< 1° of latitude/longitude) and regions (5–9°). The robustness of these patterns to spatially inconsistent sampling effort was tested using Monte Carlo‐style simulations. Levels of local endemism and species richness over numbers of samples were compared for seamount and non‐seamount areas using linear regressions. Non‐seamount populations were randomly generated from areas and depth ranges that reflected the typical sampling profile of seamounts. Results Seamount ophiuroid assemblages did not exhibit elevated levels of species richness or narrow‐range endemism compared with non‐seamount areas. Seamounts can exhibit high overall species richness for low numbers of samples, particularly on seamounts supporting a dense coral matrix, but this does not increase with additional sampling at the rates found in non‐seamount areas. There were relatively few identifiable seamount specialists. In general, seamount faunas reflected those found at similar depths in surrounding areas, including the continental slope. Seamount and non‐seamount faunas within the study area exhibited congruent latitudinal and bathymetric species turnover. Main conclusions Seamount faunas were variable for ophiuroid faunal composition, species richness and narrow‐range endemism, reflecting their environmental diversity and complex history. The continental slope was also variable, with some areas being particularly species rich. Broad geomorphological habitat categories such as ‘seamounts’ or ‘continental slope’ may be at the wrong scale to be useful for conservation planning. 相似文献
107.
Simon Dellicour Shannon Fearnley Anicée Lombal Sarah Heidl Elizabeth P. Dahlhoff Nathan E. Rank Patrick Mardulyn 《Evolution; international journal of organic evolution》2014,68(8):2371-2385
The leaf beetle Chrysomela aeneicollis occurs across Western North America, either at high elevation or in small, isolated populations along the coast, and thus has a highly fragmented distribution. DNA sequence data (three loci) were collected from five regions across the species range. Population connectivity was examined using traditional ecological niche modeling, which suggested that gene flow could occur among regions now and in the past. We developed geographically explicit coalescence models of sequence evolution that incorporated a two‐dimensional representation of the hypothesized ranges suggested by the niche‐modeling estimates. We simulated sequence data according to these models and compared them to observed sequences to identify most probable scenarios regarding the migration history of C. aeneicollis. Our results disagreed with initial niche‐modeling estimates by clearly rejecting recent connectivity among regions, and were instead most consistent with a long period of range fragmentation, extending well beyond the last glacial maximum. This application of geographically explicit models of coalescence has highlighted some limitations of the use of climatic variables for predicting the present and past range of a species and has explained aspects of the Pleistocene evolutionary history of a cold‐adapted organism in Western North America. 相似文献
108.
Use of single-sample genetic methods to estimate effective population size has skyrocketed in recent years. Although the underlying models assume discrete generations, they are widely applied to age-structured species. We simulated genetic data for 21 iteroparous animal and plant species to evaluate two untested hypotheses regarding performance of the single-sample method based on linkage disequilibrium (LD): (1) estimates based on single-cohort samples reflect the effective number of breeders in one reproductive cycle (Nb), and (2) mixed-age samples reflect the effective size per generation (Ne). We calculated true Ne and Nb, using the model species’ vital rates, and verified these with individual-based simulations. We show that single-cohort samples should be equally influenced by Nb and Ne and confirm this with simulated results: was a linear (r2 = 0.98) function of the harmonic mean of Ne and Nb. We provide a quantitative bias correction for raw based on the ratio Nb/Ne, which can be estimated from two or three simple life history traits. Bias-adjusted estimates were within 5% of true Nb for all 21 study species and proved robust when challenged with new data. Mixed-age adult samples produced downwardly biased estimates in all species, which we attribute to a two-locus Wahlund effect (mixture LD) caused by combining parents from different cohorts in a single sample. Results from this study will facilitate interpretation of rapidly accumulating genetic estimates in terms of both Ne (which influences long-term evolutionary processes) and Nb (which is more important for understanding eco-evolutionary dynamics and mating systems). 相似文献
109.
The regulation of intracellular Ca2 + triggers a multitude of vital processes in biological cells. Ca2 + permeable ryanodine receptors (RyRs) are the biggest known ion channels and play a key role in the regulation of intracellular calcium concentrations, particularly in muscle cells. In this study, we construct a computational model of the pore region of the skeletal RyR and perform molecular dynamics (MD) simulations. The dynamics and distribution of Ca2 + around the luminal pore entry of the RyR suggest that Ca2 + ions are channeled to the pore entry due to the arrangement of (acidic) amino acids at the extramembrane surface of the protein. This efficient mechanism of Ca2 + supply is thought to be part of the mechanism of Ca2 + conductance of RyRs. Viral myocarditis is predominantly caused by coxsackie viruses that induce the expression of the protein 2B which is known to affect intracellular Ca2 + homeostasis in infected cells. From our sequence comparison, it is hypothesized, that modulation of RyR could be due to replacement of its transmembrane domains (TMDs) by those domains of the viral channel forming protein 2B of coxsackie virus. This article is part of a Special Issue entitled: Viral Membrane Proteins — Channels for Cellular Networking. 相似文献
110.
The energetic cost of burying charged groups in the hydrophobic core of lipid bilayers has been controversial, with simulations giving higher estimates than certain experiments. Implicit membrane approaches are usually deemed too simplistic for this problem. Here we challenge this view. The free energy of transfer of amino acid side chains from water to the membrane center predicted by IMM1 is reasonably close to all-atom free energy calculations. The shape of the free energy profile, however, for the charged side chains needs to be modified to reflect the all-atom simulation findings (IMM1-LF). Membrane thinning is treated by combining simulations at different membrane widths with an estimate of membrane deformation free energy from elasticity theory. This approach is first tested on the voltage sensor and the isolated S4 helix of potassium channels. The voltage sensor is stably inserted in a transmembrane orientation for both the original and the modified model. The transmembrane orientation of the isolated S4 helix is unstable in the original model, but a stable local minimum in IMM1-LF, slightly higher in energy than the interfacial orientation. Peptide translocation is addressed by mapping the effective energy of the peptide as a function of vertical position and tilt angle, which allows identification of minimum energy pathways and transition states. The barriers computed for the S4 helix and other experimentally studied peptides are low enough for an observable rate. Thus, computational results and experimental studies on the membrane burial of peptide charged groups appear to be consistent. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova. 相似文献