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Mikkelsen TS Hanna J Zhang X Ku M Wernig M Schorderet P Bernstein BE Jaenisch R Lander ES Meissner A 《Nature》2008,454(7200):49-55
134.
Meissner A Mikkelsen TS Gu H Wernig M Hanna J Sivachenko A Zhang X Bernstein BE Nusbaum C Jaffe DB Gnirke A Jaenisch R Lander ES 《Nature》2008,454(7205):766-770
DNA methylation is essential for normal development and has been implicated in many pathologies including cancer. Our knowledge about the genome-wide distribution of DNA methylation, how it changes during cellular differentiation and how it relates to histone methylation and other chromatin modifications in mammals remains limited. Here we report the generation and analysis of genome-scale DNA methylation profiles at nucleotide resolution in mammalian cells. Using high-throughput reduced representation bisulphite sequencing and single-molecule-based sequencing, we generated DNA methylation maps covering most CpG islands, and a representative sampling of conserved non-coding elements, transposons and other genomic features, for mouse embryonic stem cells, embryonic-stem-cell-derived and primary neural cells, and eight other primary tissues. Several key findings emerge from the data. First, DNA methylation patterns are better correlated with histone methylation patterns than with the underlying genome sequence context. Second, methylation of CpGs are dynamic epigenetic marks that undergo extensive changes during cellular differentiation, particularly in regulatory regions outside of core promoters. Third, analysis of embryonic-stem-cell-derived and primary cells reveals that 'weak' CpG islands associated with a specific set of developmentally regulated genes undergo aberrant hypermethylation during extended proliferation in vitro, in a pattern reminiscent of that reported in some primary tumours. More generally, the results establish reduced representation bisulphite sequencing as a powerful technology for epigenetic profiling of cell populations relevant to developmental biology, cancer and regenerative medicine. 相似文献
135.
Plasmaspheric hiss is a type of electromagnetic wave found ubiquitously in the dense plasma region that encircles the Earth, known as the plasmasphere. This important wave is known to remove the high-energy electrons that are trapped along the Earth's magnetic field lines, and therefore helps to reduce the radiation hazards to satellites and humans in space. Numerous theories to explain the origin of hiss have been proposed over the past four decades, but none have been able to account fully for its observed properties. Here we show that a different wave type called chorus, previously thought to be unrelated to hiss, can propagate into the plasmasphere from tens of thousands of kilometres away, and evolve into hiss. Our new model naturally accounts for the observed frequency band of hiss, its incoherent nature, its day-night asymmetry in intensity, its association with solar activity and its spatial distribution. The connection between chorus and hiss is very interesting because chorus is instrumental in the formation of high-energy electrons outside the plasmasphere, whereas hiss depletes these electrons at lower equatorial altitudes. 相似文献
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International Consortium for Systemic Lupus Erythematosus Genetics 《Nature genetics》2008,40(2):204-210
Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with complex etiology but strong clustering in families (lambda(S) = approximately 30). We performed a genome-wide association scan using 317,501 SNPs in 720 women of European ancestry with SLE and in 2,337 controls, and we genotyped consistently associated SNPs in two additional independent sample sets totaling 1,846 affected women and 1,825 controls. Aside from the expected strong association between SLE and the HLA region on chromosome 6p21 and the previously confirmed non-HLA locus IRF5 on chromosome 7q32, we found evidence of association with replication (1.1 x 10(-7) < P(overall) < 1.6 x 10(-23); odds ratio = 0.82-1.62) in four regions: 16p11.2 (ITGAM), 11p15.5 (KIAA1542), 3p14.3 (PXK) and 1q25.1 (rs10798269). We also found evidence for association (P < 1 x 10(-5)) at FCGR2A, PTPN22 and STAT4, regions previously associated with SLE and other autoimmune diseases, as well as at > or =9 other loci (P < 2 x 10(-7)). Our results show that numerous genes, some with known immune-related functions, predispose to SLE. 相似文献
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Williams ES Stap J Essers J Ponnaiya B Luijsterburg MS Krawczyk PM Ullrich RL Aten JA Bailey SM 《Nature genetics》2007,39(6):696-8; author reply 698-9
139.
Malek RL Wang HY Kwitek AE Greene AS Bhagabati N Borchardt G Cahill L Currier T Frank B Fu X Hasinoff M Howe E Letwin N Luu TV Saeed A Sajadi H Salzberg SL Sultana R Thiagarajan M Tsai J Veratti K White J Quackenbush J Jacob HJ Lee NH 《Nature genetics》2006,38(2):234-239
Cardiovascular disorders are influenced by genetic and environmental factors. The TIGR rodent expression web-based resource (TREX) contains over 2,200 microarray hybridizations, involving over 800 animals from 18 different rat strains. These strains comprise genetically diverse parental animals and a panel of chromosomal substitution strains derived by introgressing individual chromosomes from normotensive Brown Norway (BN/NHsdMcwi) rats into the background of Dahl salt sensitive (SS/JrHsdMcwi) rats. The profiles document gene-expression changes in both genders, four tissues (heart, lung, liver, kidney) and two environmental conditions (normoxia, hypoxia). This translates into almost 400 high-quality direct comparisons (not including replicates) and over 100,000 pairwise comparisons. As each individual chromosomal substitution strain represents on average less than a 5% change from the parental genome, consomic strains provide a useful mechanism to dissect complex traits and identify causative genes. We performed a variety of data-mining manipulations on the profiles and used complementary physiological data from the PhysGen resource to demonstrate how TREX can be used by the cardiovascular community for hypothesis generation. 相似文献
140.
Rob Houtmeyers Jacob Souopgui Sabine Tejpar Ruth Arkell 《Cellular and molecular life sciences : CMLS》2013,70(20):3791-3811
The zinc finger of the cerebellum gene (ZIC) discovered in Drosophila melanogaster (odd-paired) has five homologs in Xenopus, chicken, mice, and humans, and seven in zebrafish. This pattern of gene copy expansion is accompanied by a divergence in gene and protein structure, suggesting that Zic family members share some, but not all, functions. ZIC genes are implicated in neuroectodermal development and neural crest cell induction. All share conserved regions encoding zinc finger domains, however their heterogeneity and specification remain unexplained. In this review, the evolution, structure, and expression patterns of the ZIC homologs are described; specific functions attributable to individual family members are supported. A review of data from functional studies in Xenopus and murine models suggest that ZIC genes encode multifunctional proteins operating in a context-specific manner to drive critical events during embryogenesis. The identification of ZIC mutations in congenital syndromes highlights the relevance of these genes in human development. 相似文献