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121.
Subir K. Das 《Molecular simulation》2015,41(5-6):382-401
We review a few simulation methods and results related to the structure and non-equilibrium dynamics in the coexistence region of immiscible symmetric binary fluids, in bulk as well as under confinement, with special emphasis on the latter. Monte Carlo methods to estimate interfacial tensions for flat and curved interfaces have been discussed. The latter, combined with a thermodynamic integration technique, provides contact angles for coexisting fluids attached to the wall. For such three-phase coexistence, results for the line tension are also presented. For the kinetics of phase separation, various mechanisms and corresponding theoretical expectations have been discussed. A comparative picture between the domain growth in bulk and confinement (including thin-film and semi-infinite geometry) has been presented from molecular dynamics simulations. Applications of finite-size scaling technique have been discussed in both equilibrium and non-equilibrium contexts. 相似文献
122.
123.
Yuka Kobayashi Norikazu Kiguchi Yohji Fukazawa Fumihiro Saika Takehiko Maeda Shiroh Kishioka 《The Journal of biological chemistry》2015,290(20):12603-12613
Peripheral neuroinflammation caused by activated immune cells can provoke neuropathic pain. Herein, we investigate the actions of macrophages and T cells through glucocorticoid-induced tumor neurosis factor receptor ligand (GITRL) and its receptor (GITR) in neuropathic pain. After partial sciatic nerve ligation (PSL) in enhanced green fluorescent protein (eGFP) chimeric mice generated by the transplantation of eGFP+ bone marrow cells, eGFP+ macrophages, and T cells markedly migrated to the injured site after PSL. Administration of agents to deplete macrophages (liposome-clodronate and Clophosome-ATM) or T cells (anti-CD4 antibody and FTY720) could suppress PSL-induced thermal hyperalgesia and tactile allodynia. The expression levels of co-stimulatory molecules GITRL and GITR were increased on infiltrating macrophages and T cells, respectively. The perineural injection of a GITRL neutralizing antibody that could inhibit the function of the GITRL-GITR pathway attenuated PSL-induced neuropathic pain. Additionally, the induction of inflammatory cytokines and the accumulation of GITR+ T cells in the injured SCN were abrogated after macrophage depletion by Clophosome-ATM. In conclusion, GITRL expressed on macrophages drives cytokine release and T cell activation, resulting in neuropathic pain via GITR-dependent actions. The GITRL-GITR pathway might represent a novel target for the treatment of neuropathic pain. 相似文献
124.
Natalia Kirichenko Peter Huemer Helmut Deutsch Paolo Triberti Rodolphe Rougerie Carlos Lopez-Vaamonde 《ZooKeys》2015,(473):157-176
Europe has one of the best-known Lepidopteran faunas in the world, yet many species are still being discovered, especially in groups of small moths. Here we describe a new gracillariid species from the south-eastern Alps, Callisto
basistrigella Huemer, Deutsch & Triberti, sp. n. It shows differences from its sister species Callisto
coffeella in morphology, the barcode region of the cytochrome c oxidase I gene and the nuclear gene histone H3. Both Callisto
basistrigella and Callisto
coffeella can co-occur in sympatry without evidence of admixture. Two Callisto
basistrigella specimens show evidence of introgression. We highlight the importance of an integrative approach to delimit species, combining morphological and ecological data with mitochondrial and nuclear sequence data. Furthermore, in connection with this study, Ornix
blandella Müller-Rutz, 1920, syn. n. is synonymized with Callisto
coffeella (Zetterstedt, 1839). 相似文献
125.
Inken Pedall Uwe Fritz Heiko Stuckas Aitor Valdeón Michael Wink 《Journal of Zoological Systematics and Evolutionary Research》2011,49(1):44-57
European pond turtles represent a phylogeographically deeply structured complex of distinct taxa. Here, we use mitochondrial DNA sequences (cytochrome b gene) and eight polymorphic microsatellite loci to investigate genetic differentiation and gene flow of Sicilian, Corsican and Sardinian pond turtles and of subspecies involved in two secondary contact zones in the Pyrenean region and Southern Italy. Mitochondrial and microsatellite differentiation is largely concordant in populations from the core regions of the distribution ranges of the studied taxa. Both marker systems provide no evidence for gene flow between Sicilian pond turtles (Emys trinacris) and Southern Italian subspecies of E. orbicularis. By contrast, in the contact zones limited gene flow occurs between distinct subspecies of E. orbicularis. Although the Southern Italian contact zone is significantly older than the Pyrenean contact zone of Holocene age, patterns of asymmetric introgression are similar. Introgressive hybridization leads to the exchange of mitochondria, but microsatellite data indicate only a few individuals with mixed ancestry. This suggests that incipient isolating mechanisms maintain largely discrete nuclear genomic gene pools. Furthermore, this implies that Southern Italy acted as a hotspot rather than as a melting pot of genetic diversity during the last glacial. Pond turtles from Corsica and Sardinia are not differentiated from continental populations of the subspecies E. o. galloitalica, neither in the mitochondrial nor in the quickly evolving microsatellite markers. As the fossil record argues for a continuous presence of pond turtles on both islands since the Middle Pleistocene, this suggests that the native island populations became extinct and the extant turtles were later introduced by prehistoric settlers. The lack of genetic differentiation of pond turtles from Corsica and Sardinia supports the view that the subspecies described from these islands are not valid. 相似文献
126.
Computational protein structure prediction remains a challenging task in protein bioinformatics. In the recent years, the importance of template-based structure prediction is increasing because of the growing number of protein structures solved by the structural genomics projects. To capitalize the significant efforts and investments paid on the structural genomics projects, it is urgent to establish effective ways to use the solved structures as templates by developing methods for exploiting remotely related proteins that cannot be simply identified by homology. In this work, we examine the effect of using suboptimal alignments in template-based protein structure prediction. We showed that suboptimal alignments are often more accurate than the optimal one, and such accurate suboptimal alignments can occur even at a very low rank of the alignment score. Suboptimal alignments contain a significant number of correct amino acid residue contacts. Moreover, suboptimal alignments can improve template-based models when used as input to Modeller. Finally, we use suboptimal alignments for handling a contact potential in a probabilistic way in a threading program, SUPRB. The probabilistic contacts strategy outperforms the partly thawed approach, which only uses the optimal alignment in defining residue contacts, and also the re-ranking strategy, which uses the contact potential in re-ranking alignments. The comparison with existing methods in the template-recognition test shows that SUPRB is very competitive and outperforms existing methods. 相似文献
127.
Single chain fragment variables (ScFvs) have been extensively employed in studying the protein-protein interactions. ScFvs derived from phage display libraries have an additional advantage of being generated against a native antigen, circumventing loss of information on conformational epitopes. In the present study, an attempt has been made to elucidate human chorionic gonadotropin (hCG)-luteinizing hormone (LH) receptor interactions by using a neutral and two inhibitory ScFvs against hCG. The objective was to dock a computationally derived model of these ScFvs onto the crystal structure of hCG and understand the differential roles of the mapped epitopes in hCG-LH receptor interactions. An anti-hCG ScFv, whose epitope was mapped previously using biochemical tools, served as the positive control for assessing the quality of docking analysis. To evaluate the role of specific side chains at the hCG-ScFv interface, binding free energy as well as residue interaction energies of complexes in solution were calculated using molecular mechanics Poisson-Boltzmann/surface area method after performing the molecular dynamic simulations on the selected hCG-ScFv models and validated using biochemical and SPR analysis. The robustness of these calculations was demonstrated by comparing the theoretically determined binding energies with the experimentally obtained kinetic parameters for hCG-ScFv complexes. Superimposition of hCG-ScFv model onto a model of hCG complexed with the 51-266 residues of LH receptor revealed importance of the residues previously thought to be unimportant for hormone binding and response. This analysis provides an alternate tool for understanding the structure-function analysis of ligand-receptor interactions. 相似文献
128.
Huang KY Amodeo GA Tong L McDermott A 《Protein science : a publication of the Protein Society》2011,20(3):630-639
A new crystal structure of human ubiquitin is reported at 1.8 Å resolution. Compared with the other known crystal structure or the solution NMR structure of monomeric human ubiquitin, this new structure is similar in its overall fold but differs with respect to the conformation of the backbone in a surface‐exposed region. The conformation reported here resembles conformations previously seen in complex with deubiquinating enzymes, wherein the Asp52/Gly53 main chain and Glu24 side chain move. This movement exposes the backbone carbonyl of Asp52 to the exterior of the molecule, making it possible to engage in hydrogen‐bond contacts with neighboring molecules, rather than in an internal hydrogen bond with the backbone of Glu24. This particular crystal form of ubiquitin has been used in a large number of solid state NMR studies. The structure described here elucidates the origin of many of the chemical shift differences comparing solution and solid state studies. 相似文献
129.
Forse GJ Ram N Banatao DR Cascio D Sawaya MR Klock HE Lesley SA Yeates TO 《Protein science : a publication of the Protein Society》2011,20(1):168-178
Protein crystallization continues to be a major bottleneck in X‐ray crystallography. Previous studies suggest that symmetric proteins, such as homodimers, might crystallize more readily than monomeric proteins or asymmetric complexes. Proteins that are naturally monomeric can be made homodimeric artificially. Our approach is to create homodimeric proteins by introducing single cysteines into the protein of interest, which are then oxidized to form a disulfide bond between the two monomers. By introducing the single cysteine at different sequence positions, one can produce a variety of synthetically dimerized versions of a protein, with each construct expected to exhibit its own crystallization behavior. In earlier work, we demonstrated the potential utility of the approach using T4 lysozyme as a model system. Here we report the successful application of the method to Thermotoga maritima CelA, a thermophilic endoglucanase enzyme with low sequence identity to proteins with structures previously reported in the Protein Data Bank. This protein had resisted crystallization in its natural monomeric form, despite a broad survey of crystallization conditions. The synthetic dimerization of the CelA mutant D188C yielded well‐diffracting crystals with molecules in a packing arrangement that would not have occurred with native, monomeric CelA. A 2.4 Å crystal structure was determined by single anomalous dispersion using a seleno‐methionine derivatized protein. The results support the notion that synthetic symmetrization can be a useful approach for enlarging the search space for crystallizing monomeric proteins or asymmetric complexes. 相似文献
130.