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991.
Lucia Kwan Howard D. Rundle 《Evolution; international journal of organic evolution》2010,64(3):710-723
Many laboratory speciation experiments have raised allopatric populations in different environments to determine whether reproductive isolation evolves as a byproduct of adaptation (a form of ecological speciation). Few, however, have addressed the evolution of both pre‐ and postmating isolation or investigated the conditions affecting the process. We present results of an evolution experiment in which 12 lines of Drosophila melanogaster were derived from a common population and then independently evolved for more than 57 generations under alternative selection treatments. Six “desiccation” populations had access to food and water removed during a period of their adult lives generating strong desiccation selection, and six “starvation” populations had access to food but not water removed for the same period, generating a mild starvation stress. Substantial divergence of cuticular hydrocarbons occurred between the desiccation and starvation populations, key traits that have been implicated in sexual isolation in Drosophila. Despite this divergence, there was no detectable premating isolation between desiccation and starvation populations and postmating isolation was asymmetrical: the fitness of F1 hybrids was reduced in the desiccation but not the starvation environment. This asymmetry was likely caused by the absence of divergent selection: adaptation to desiccation appears to have come at no cost to performance in the starvation environment. Novel environments are thought to promote the evolution of reproductive isolation. Understanding the conditions that favor or hamper this remains a key challenge for speciation research. 相似文献
992.
Huanchen Wang Howard Robinson Hengming Ke 《The Journal of biological chemistry》2010,285(49):38149-38156
The activity of phosphodiesterase-5 (PDE5) is specific for cGMP and is regulated by cGMP binding to GAF-A in its regulatory domain. To better understand the regulatory mechanism, x-ray crystallographic and biochemical studies were performed on constructs of human PDE5A1 containing the N-terminal phosphorylation segment, GAF-A, and GAF-B. Superposition of this unliganded GAF-A with the previously reported NMR structure of cGMP-bound PDE5 revealed dramatic conformational differences and suggested that helix H4 and strand B3 probably serve as two lids to gate the cGMP-binding pocket in GAF-A. The structure also identified an interfacial region among GAF-A, GAF-B, and the N-terminal loop, which may serve as a relay of the cGMP signal from GAF-A to GAF-B. N-terminal loop 98–147 was physically associated with GAF-B domains of the dimer. Biochemical analyses showed an inhibitory effect of this loop on cGMP binding and its involvement in the cGMP-induced conformation changes. 相似文献
993.
Merryman WD Youn I Lukoff HD Krueger PM Guilak F Hopkins RA Sacks MS 《American journal of physiology. Heart and circulatory physiology》2006,290(1):H224-H231
It has been speculated that heart valve interstitial cells (VICs) maintain valvular tissue homeostasis through regulated extracellular matrix (primarily collagen) biosynthesis. VICs appear to be phenotypically plastic, inasmuch as they transdifferentiate into myofibroblasts during valve development, disease, and remodeling. Under normal physiological conditions, transvalvular pressures (TVPs) on the right and left side of the heart are vastly different. Hence, we hypothesize that higher left-side TVPs impose larger local tissue stress on VICs, which increases their stiffness through cytoskeletal composition, and that this relation affects collagen biosynthesis. To evaluate this hypothesis, isolated ovine VICs from the four heart valves were subjected to micropipette aspiration to assess cellular stiffness, and cytoskeletal composition and collagen biosynthesis were quantified by using the surrogates smooth muscle alpha-actin (SMA) and heat shock protein 47 (HSP47), respectively. VICs from the aortic and mitral valves were significantly stiffer (P < 0.001) than those from the pulmonary and tricuspid valves. Left-side isolated VICs contained significantly more (P < 0.001) SMA and HSP47 than right-side VICs. Mean VIC stiffness correlated well (r = 0.973) with TVP; SMA and HSP47 also correlated well (r = 0.996) with one another. Assays were repeated for VICs in situ, and, as with in vitro results, left-side VIC protein levels were significantly greater (P < 0.05). These findings suggest that VICs respond to local tissue stress by altering cellular stiffness (through SMA content) and collagen biosynthesis. This functional VIC stress-dependent biosynthetic relation may be crucial in maintaining valvular tissue homeostasis and also prove useful in understanding valvular pathologies. 相似文献
994.
Schlick NE Jensen-Seaman MI Orlebeke K Kwitek AE Jacob HJ Lazar J 《American journal of physiology. Cell physiology》2006,291(6):C1183-C1192
Rat remains a major biomedical model system for common, complex diseases. The rat continues to gain importance as a model system with the completion of its full genomic sequence. Although the genomic sequence has generated much interest, only three complete sequences of the rat mitochondria exist. Therefore, to increase the knowledge of the rat genome, the entire mitochondrial genomes (16,30716,315 bp) from 10 inbred rat strains (that are standard laboratory models around the world) and 2 wild rat strains were sequenced. We observed a total of 195 polymorphisms, 32 of which created an amino acid change (nonsynonymous substitutions) in 12 of the 13 protein coding genes within the mitochondrial genome. There were 11 single nucleotide polymorphisms within the tRNA genes, six in the 12S rRNA, and 12 in the 16S rRNA including 3 insertions/deletions. We found 14 single nucleotide polymorphisms and 2 insertion/deletion polymorphisms in the D-loop. The inbred rat strains cluster phylogenetically into three distinct groups. The wild rat from Tokyo grouped closely with five inbred strains in the phylogeny, whereas the wild rat from Milwaukee was not closely related to any inbred strain. These data will enable investigators to rapidly assess the potential impact of the mitochondria in these rats on the physiology and the pathophysiology of phenotypes studied in these strains. Moreover, these data provide information that may be useful as new animal models, which result in novel combinations of nuclear and mitochondrial genomes, are developed. genome; mitochondria 相似文献
995.
In a continuous T-maze alternation task, CA1 complex-spike neurons in the hippocampus differentially fire as the rat traverses overlapping segments of the maze (i.e., the stem) repeatedly via alternate routes. The temporal dynamics of this phenomenon were further investigated in the current study. Rats learned the alternation task from the first day of acquisition and the differential firing pattern in the stem was observed accordingly. More importantly, we report a phenomenon in which spatial correlates of CA1 neuronal ensembles gradually changed from their original firing locations, shifting toward prospective goal locations in the continuous T-maze alternation task. The relative locations of simultaneously recorded firing fields, however, were preserved within the ensemble spatial representation during this shifting. The within-session shifts in preferred firing locations in the absence of any changes in the environment suggest that certain cognitive factors can significantly alter the location-bound coding scheme of hippocampal neurons. 相似文献
996.
VC0702, a conserved hypothetical protein of unknown function from Vibrio cholerae, resides in a three-gene operon containing the MbaA gene that encodes for a GGDEF and EAL domain-containing protein which is involved in regulating formation of the extracellular matrix of biofilms in Vibrio cholerae. The VC0702 crystal structure has been determined at 2.0 A and refined to Rwork = 22.8% and Rfree = 26.3%. VC0702 crystallized in an orthorhombic crystal lattice in the C222(1) space group with dimensions of a = 66.61 A, b = 88.118 A, and c = 118.35 A with a homodimer in the asymmetric unit. VC0702, which forms a mixed alpha + beta three-layered alphabetaalpha sandwich, belongs to the Pfam DUF84 and COG1986 families of proteins. Sequence conservation within the DUF84 and COG1986 families was used to identify a conserved patch of surface residues that define a cleft and potential substrate-binding site in VC0702. The three-dimensional structure of VC0702 is similar to that of Mj0226 from Methanococcus janeschii, which has been identified as a novel NTPase that binds NTP in a deep cleft similarly located to the conserved patch of surface residues that define an analogous cleft in VC0702. Collectively, the data suggest that VC0702 may have a biochemical function that involves NTP binding and phosphatase activity of some kind, and is likely involved in regulation of the signaling pathway that controls biofilm formation and maintenance in Vibrio cholerae. 相似文献
997.
Howard RW 《Journal of biosocial science》2006,38(3):423-426
Bilalic and McLeod's arguments fall short on several grounds.There are excellent logical reasons to expect strong ability/chess expertise links and specific research evidence to date is sparse, with mixed findings. Data are presented from Georgia, which has a high female participation rate in chess, which suggest that differing gender motivation levels and participation rates impact relatively little on chess performance differences at the extreme. 相似文献
998.
Karni A Abraham M Monsonego A Cai G Freeman GJ Hafler D Khoury SJ Weiner HL 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(6):4196-4202
Multiple sclerosis (MS) is postulated to be a T cell-mediated autoimmune disease characterized clinically by a relapsing-remitting (RR) stage followed by a secondary progressive (SP) phase. The progressive phase is felt to be secondary to neuronal degenerative changes triggered by inflammation. The status of the innate immune system and its relationship to the stages of MS is not well understood. Dendritic cells (DCs) are professional APCs that are central cells of the innate immune system and have the unique capacity to induce primary immune responses. We investigated circulating myeloid DCs isolated directly from the blood to determine whether there were abnormalities in myeloid DCs in MS and whether they were related to disease stage. We found that SP-MS subjects had an increased percentage of DCs expressing CD80, a decreased percentage expressing PD-L1, and an increased percentage producing IL-12 and TNF-alpha compared with RR-MS or controls. A higher percentage of DCs from both RR and SP-MS patients expressed CD40 compared with controls. We then investigated the polarization effect of DCs from MS patients on naive T cells taken from cord blood using a MLR assay. Whereas DCs from RR-MS induced higher levels of Th1 (IFN-gamma, TNF-alpha) and Th2 (IL-4, IL-13) cytokines compared with controls, DCs from SP-MS only induced a polarized Th1 response. These results demonstrate abnormalities of DCs in MS and may explain the immunologic basis for the different stages and clinical patterns of MS. 相似文献
999.
Edwards JP Bell HA Audsley N Marris GC Kirkbride-Smith A Bryning G Frisco C Cusson M 《Journal of insect physiology》2006,52(11-12):1153-1162
To successfully complete its development, the gregarious ectoparasitoid Eulophus pennicornis must inhibit the moult of its host, Lacanobia oleracea. In the present study, we examined the possibility that moult- and metamorphosis-associated endocrine events may be disrupted in caterpillars parasitized as newly moulted last (sixth) instars. Juvenile hormone (JH) titres on days 2 and 5 of the final stadium were significantly higher (> 100 fold) in parasitized than in non-parasitized hosts, in which JH was essentially absent. Elevated JH levels were associated with reduced haemolymph JH esterase (JHE) activity (down by 99.8%) and enhanced in vitro JH biosynthesis by the corpora allata (CA) (up to 4.5 fold). Wasp adults and/or larvae, in which we measured high levels of JH III (up to 2.7 ng/g), but little or no JH I or JH II, were not seen as likely sources of JH in parasitized hosts, in which we found mostly JH I and JH II. In addition, removal of parasitoid eggs or larvae after oviposition did not prevent the rise in JH titres seen in parasitoid-laden hosts, suggesting that wasp venom may be responsible for the observed hormonal dysfunction. Host haemolymph 20-hydroxyecdysone (20-E) levels were largely unaffected by parasitism during the final stadium although they were observed to increase earlier and decrease more rapidly in parasitized insects. We compare these results with those reported earlier for L. oleracea larvae parasitized by E. pennicornis as penultimate (fifth) instars, which display significantly depressed 20-E titres relative to control larvae. We conclude that E. pennicornis employs host endocrine-disruption strategies that differ according to whether the host is parasitized as a penultimate or final-stadium larva. 相似文献
1000.
IL-23 is increased in dendritic cells in multiple sclerosis and down-regulation of IL-23 by antisense oligos increases dendritic cell IL-10 production 总被引:15,自引:0,他引:15
Vaknin-Dembinsky A Balashov K Weiner HL 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(12):7768-7774
IL-23 is a heterodimeric cytokine comprising a p19 subunit associated with the IL-12/23p40 subunit. Like IL-12, IL-23 is expressed predominantly by activated dendritic cells (DCs) and phagocytic cells, and both cytokines induce IFN-gamma secretion by T cells. The induction of experimental autoimmune encephalitis, the animal model of multiple sclerosis (MS), occurs in mice lacking IL-12, but not in mice with targeted disruption of IL-23 or both IL-12 and IL-23. Thus, IL-23 expression in DCs may play an important role in the pathogenesis of human autoimmune diseases such as MS. We quantified the expression of IL-23 in monocyte-derived DCs in MS patients and healthy donors and found that DCs from MS patients secrete elevated amounts of IL-23 and express increased levels of IL-23p19 mRNA. Consistent with this abnormality, we found increased IL-17 production by T cells from MS patients. We then transfected monocyte-derived DCs from healthy donors with antisense oligonucleotides specific for the IL-23p19 and IL-12p35 genes and found potent suppression of gene expression and blockade of bioactive IL-23 and IL-12 production without affecting cellular viability or DCs maturation. Inhibition of IL-23 and IL-12 was associated with increased IL-10 and decreased TNF-alpha production. Furthermore, transfected DCs were poor allostimulators in the MLR. Our results demonstrate that an abnormal Th1 bias in DCs from MS patients related to IL-23 exists, and that antisense oligonucleotides specific to IL-23 can be used for immune modulation by targeting DC gene expression. 相似文献