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991.
Mapping early brain development in autism 总被引:3,自引:0,他引:3
Courchesne E Pierce K Schumann CM Redcay E Buckwalter JA Kennedy DP Morgan J 《Neuron》2007,56(2):399-413
Although the neurobiology of autism has been studied for more than two decades, the majority of these studies have examined brain structure 10, 20, or more years after the onset of clinical symptoms. The pathological biology that causes autism remains unknown, but its signature is likely to be most evident during the first years of life when clinical symptoms are emerging. This review highlights neurobiological findings during the first years of life and emphasizes early brain overgrowth as a key factor in the pathobiology of autism. We speculate that excess neuron numbers may be one possible cause of early brain overgrowth and produce defects in neural patterning and wiring, with exuberant local and short-distance cortical interactions impeding the function of large-scale, long-distance interactions between brain regions. Because large-scale networks underlie socio-emotional and communication functions, such alterations in brain architecture could relate to the early clinical manifestations of autism. As such, autism may additionally provide unique insight into genetic and developmental processes that shape early neural wiring patterns and make possible higher-order social, emotional, and communication functions. 相似文献
992.
Edwin G. Peery Michael D. Elmore James L. Resnick Camilynn I. Brannan Karen A. Johnstone 《Mammalian genome》2007,18(4):255-262
Prader-Willi syndrome (PWS) and Angelman syndrome (AS) result from the disturbance of imprinted gene expression within human
chromosome 15q11–q13. Some cases of PWS and AS are caused by microdeletions near the SNRPN gene that disrupt a regulatory element termed the imprinting center (IC). The IC has two functional components; an element
at the promoter of SNRPN involved in PWS (PWS-IC) and an element 35 kilobases (kb) upstream of SNRPN involved in AS (AS-IC). To further understand the function of the IC, we sought to create a mouse model for AS-IC mutations.
We have generated two deletions at a location analogous to that of the human AS-IC. Neither deletion produced an imprinting
defect as indicated by DNA methylation and gene expression analyses. These results indicate that no elements critical for
AS-IC function in mouse reside within the 12.8-kb deleted region and suggest that the specific location of the AS-IC is not
conserved between human and mouse.
Camilynn I. Brannan was Deceased 相似文献
993.
Sugiura K Su YQ Diaz FJ Pangas SA Sharma S Wigglesworth K O'Brien MJ Matzuk MM Shimasaki S Eppig JJ 《Development (Cambridge, England)》2007,134(14):2593-2603
Mammalian oocytes are deficient in their ability to carry out glycolysis. Therefore, the products of glycolysis that are necessary for oocyte development are provided to oocytes by companion cumulus cells. Mouse oocytes secrete paracrine factors that promote glycolysis in cumulus cells. The objective of this study was to identify paracrine factors secreted by oocytes that promote glycolysis and expression of mRNA encoding the glycolytic enzymes PFKP and LDHA. Candidates included growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15) and fibroblast growth factors (FGFs). Bmp15-/- and Gdf9+/- Bmp15-/- (double mutant, DM) cumulus cells exhibited reduced levels of both glycolysis and Pfkp and Ldha mRNA, and mutant oocytes were deficient in promoting glycolysis and expression of Pfkp and Ldha mRNA in cumulus cells of wild-type (WT) mice. Alone, neither recombinant BMP15, GDF9 nor FGF8 promoted glycolysis and expression of Pfkp and Ldha mRNA in WT cumulus cells. Co-treatment with BMP15 and FGF8 promoted glycolysis and increased expression of Pfkp and Ldha mRNA in WT cumulus cells to the same levels as WT oocytes; however, the combinations of BMP15/GDF9 or GDF9/FGF8 did not. Furthermore, SU5402, an FGF receptor-dependent protein kinase inhibitor, inhibited Pfkp and Ldha expression in cumulus cells promoted by paracrine oocyte factors. Therefore, oocyte-derived BMP15 and FGFs cooperate to promote glycolysis in cumulus cells. 相似文献
994.
Pittman MS Elvers KT Lee L Jones MA Poole RK Park SF Kelly DJ 《Molecular microbiology》2007,63(2):575-590
Pathways of electron transport to periplasmic nitrate (NapA) and nitrite (NrfA) reductases have been investigated in Campylobacter jejuni, a microaerophilic food-borne pathogen. The nap operon is unusual in lacking napC (encoding a tetra-haem c-type cytochrome) and napF, but contains a novel gene of unknown function, napL. The iron-sulphur protein NapG has a major role in electron transfer to the NapAB complex, but we show that slow nitrate-dependent growth of a napG mutant can be sustained by electron transfer from NrfH, the electron donor to the nitrite reductase NrfA. A napL mutant possessed approximately 50% lower NapA activity than the wild type but showed normal growth with nitrate as the electron acceptor. NrfA was constitutive and was shown to play a role in protection against nitrosative stress in addition to the previously identified NO-inducible single domain globin, Cgb. However, nitrite also induced cgb expression in an NssR-dependent manner, suggesting that growth of C. jejuni with nitrite causes nitrosative stress. This was confirmed by lack of growth of cgb and nssR mutants, and slow growth of the nrfA mutant, in media containing nitrite. Thus, NrfA and Cgb together provide C. jejuni with constitutive and inducible components of a robust defence against nitrosative stress. 相似文献
995.
996.
Background
With the increased availability of high throughput data, such as DNA microarray data, researchers are capable of producing large amounts of biological data. During the analysis of such data often there is the need to further explore the similarity of genes not only with respect to their expression, but also with respect to their functional annotation which can be obtained from Gene Ontology (GO).Results
We present the freely available software package GOSim, which allows to calculate the functional similarity of genes based on various information theoretic similarity concepts for GO terms. GOSim extends existing tools by providing additional lately developed functional similarity measures for genes. These can e.g. be used to cluster genes according to their biological function. Vice versa, they can also be used to evaluate the homogeneity of a given grouping of genes with respect to their GO annotation. GOSim hence provides the researcher with a flexible and powerful tool to combine knowledge stored in GO with experimental data. It can be seen as complementary to other tools that, for instance, search for significantly overrepresented GO terms within a given group of genes.Conclusion
GOSim is implemented as a package for the statistical computing environment R and is distributed under GPL within the CRAN project. 相似文献997.
Karen Goossens Ann Van Soom Mario Van Poucke Leen Vandaele Jo Vandesompele Alex Van Zeveren Luc J Peelman 《BMC developmental biology》2007,7(1):64
Background
Normal preimplantation embryo development encompasses a series of events including first cleavage division, activation of the embryonic genome, compaction and blastocyst formation. 相似文献998.
Edgcomb VP Molyneaux SJ Böer S Wirsen CO Saito M Atkins MS Lloyd K Teske A 《Extremophiles : life under extreme conditions》2007,11(2):329-342
Growth and survival of hyperthermophilic archaea in their extreme hydrothermal vent and subsurface environments are controlled
by chemical and physical key parameters. This study examined the effects of elevated sulfide concentrations, temperature,
and acidic pH on growth and survival of two hydrothermal vent archaea (Pyrococcus strain GB-D and Thermococcus fumicolans) under high temperature and pressure regimes. These two strains are members of the Thermococcales, a family of hyperthermophilic,
heterotrophic, sulfur-reducing archaea that occur in high densities at vent sites. As actively growing cells, these two strains
tolerated regimes of pH, pressure, and temperature that were in most cases not tolerated under severe substrate limitation.
A moderate pH of 5.5–7 extends their survival and growth range over a wider range of sulfide concentrations, temperature and
pressure, relative to lower pH conditions. T. fumicolans and Pyrococcus strain GB-D grew under very high pressures that exceeded in-situ pressures typical of hydrothermal vent depths, and included
deep subsurface pressures. However, under the same conditions, but in the absence of carbon substrates and electron acceptors,
survival was generally lower, and decreased rapidly when low pH stress was combined with high pressure and high temperature.
Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users. 相似文献
999.
p53 functions to prevent malignant progression, in part by inhibiting proliferation or inducing the death of potential tumour cells. One of the most important regulators of p53 is MDM2, a RING domain E3 ligase that ubiquitinates p53, leading to both proteasomal degradation and relocation of p53 from the nucleus to the cytoplasm. Previous studies have suggested that although polyubiquitination is required for degradation, monoubiquitination of p53 is sufficient for nuclear export. Using a p53-ubiquitin fusion protein we show that ubiquitination contributes to two steps before export: exposure of a carboxy-terminal nuclear export sequence (NES), and dissociation of MDM2. Monoubiquitination can directly promote further modifications of p53 with ubiquitin-like proteins and MDM2 promotes the interaction of the SUMO E3 ligase PIASy with p53, enhancing both sumoylation and nuclear export. Our results suggest that modifications such as sumoylation can regulate the strength of the p53-MDM2 interaction and participate in driving the export of p53. 相似文献
1000.
Vikhanskaya F Toh WH Dulloo I Wu Q Boominathan L Ng HH Vousden KH Sabapathy K 《Nature cell biology》2007,9(6):698-705