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991.
992.
Hundreds of variants clustered in genomic loci and biological pathways affect human height 总被引:2,自引:0,他引:2
Lango Allen H Estrada K Lettre G Berndt SI Weedon MN Rivadeneira F Willer CJ Jackson AU Vedantam S Raychaudhuri S Ferreira T Wood AR Weyant RJ Segrè AV Speliotes EK Wheeler E Soranzo N Park JH Yang J Gudbjartsson D Heard-Costa NL Randall JC Qi L Vernon Smith A Mägi R Pastinen T Liang L Heid IM Luan J Thorleifsson G Winkler TW Goddard ME Sin Lo K Palmer C Workalemahu T Aulchenko YS Johansson A Zillikens MC Feitosa MF Esko T Johnson T Ketkar S Kraft P Mangino M Prokopenko I Absher D Albrecht E 《Nature》2010,467(7317):832-838
Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P?0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways. 相似文献
993.
The influence of aging on the microstructure and mechanical properties of Cu-11.6wt%Al-3.9wt%Ni-2.5wt%Mn shape memory alloy (SMA) was studied by means of scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffractometer, and differential scanning calorimeter (DSC). Experimental results show that bainite, γ2, and α phase precipitates occur with the aging effect in the alloy. After aging at 300dgC, the bainitic precipitates appear at the early stages of aging, while the precipitates of γ2 phase are observed for a longer aging time. When the aging temperature increases, the bainite gradually evolves into γ2 phase and equilibrium α phase (bcc) precipitates from the remaining parent phase. Thus, the bainite, γ2, and α phases appear, while the martensite phase disappears progressively in the alloy. The bainitic precipitates decrease the reverse transformation temperature while the γ2 phase precipitates increase these temperatures with a decrease of solute content in the retained parent phase. On the other hand, these precipitations cause an increasing in hardness of the alloy. 相似文献
994.
995.
Chourrout D Delsuc F Chourrout P Edvardsen RB Rentzsch F Renfer E Jensen MF Zhu B de Jong P Steele RE Technau U 《Nature》2006,442(7103):684-687
Bilaterian animals have a Hox gene cluster essential for patterning the main body axis, and a ParaHox gene cluster. Comparison of Hox and ParaHox genes has led workers to postulate that both clusters originated from the duplication of an ancient cluster named ProtoHox, which contained up to four genes with at least the precursors of anterior and posterior Hox/ParaHox genes. However, the way in which genes diversified within the ProtoHox, Hox and ParaHox clusters remains unclear because no systematic study of non-bilaterian animals exists. Here we characterize the full Hox/ParaHox gene complements and genomic organization in two cnidarian species (Nematostella vectensis and Hydra magnipapillata), and suggest a ProtoHox cluster simpler than originally thought on the basis of three arguments. First, both species possess bilaterian-like anterior Hox genes, but their non-anterior genes do not appear as counterparts of either bilaterian central or posterior genes; second, two clustered ParaHox genes, Gsx and a gene related to Xlox and Cdx, are found in Nematostella vectensis; and third, we do not find clear phylogenetic support for a common origin of bilaterian Cdx and posterior genes, which might therefore have appeared after the ProtoHox cluster duplication. Consequently, the ProtoHox cluster might have consisted of only two anterior genes. Non-anterior genes could have appeared independently in the Hox and ParaHox clusters, possibly after the separation of bilaterians and cnidarians. 相似文献
996.
G. Csaba Z. Darvas R. Swydan S. U. Nagy 《Cellular and molecular life sciences : CMLS》1985,41(3):392-393
Summary Digoxin was demonstrated inTetrahymena pyriformis by radioimmunoassay, at a concentration of 4.3 ng/100,000 cells. Pretreatment of the cells with digoxin or ouabain did not significantly alter the digoxin concentration of the progeny generations. 相似文献
997.
大斜视角SAR成像的改进频率变标算法 总被引:2,自引:0,他引:2
首先给出了一种改进的频率变标算法。该算法适用于处理距离解线调后的聚束式SAR数据。对大斜視角数据,由于二次距离压缩误差的影响,偏离参考距离的散射点未能完全聚焦,且离参考距离越远聚焦性能越差。将非线性变标的方法加入频率变标算法对数据进行二次距离压缩,有效地减小了距离压缩误差。最后通过仿真实验表明,对给定的SAR参数,在斜视角为定值时,也能得到较好的成像结果。 相似文献
998.
Lower receptor avidity required for thymic clonal deletion than for effector T-cell function. 总被引:19,自引:0,他引:19
Clonal deletion in the thymus plays a major part in T-cell tolerance to self antigens. But the mechanism of negative selection, its fine specificity and the threshold of affinity and avidity remains unknown. We have now examined these aspects of negative selection with mice expressing a transgenic T-cell receptor with specificity for lymphocytic choriomeningitis virus (LCMV) glycoprotein in association with the class I H-2Db molecule. These mice were rendered tolerant to LCMV by neonatal infection with mutant LCMVs bearing point mutations in the T-cell epitope recognized by the transgenic T-cell receptor. Variant LCMVs were also tested for their ability to elicit antiviral responses in transgenic mice in vivo and in vitro. Comparison in vivo revealed that a low-avidity receptor interaction, which was unable to induce effector T cells in the periphery, was still sufficient for clonal deletion in the thymus. 相似文献
999.
Endothelial cells as part of a vascular oxygen-sensing system: hypoxia-induced release of autacoids 总被引:2,自引:0,他引:2
U Pohl 《Experientia》1990,46(11-12):1175-1179
Higher developed organisms are equipped with many central and local control mechanisms, which enable an adequate blood and oxygen supply to tissues over a wide range of demands. Global adaptive responses include changes in the circulatory and ventilatory system as well as increases in the oxygen carrying capacity of the blood. At the level of the specialized organs there exist additional control systems for the regulation of local blood flow. Most systems make use of highly specialized cells which are able to sense the oxygen partial pressure of the transport medium, blood, and within the tissues. In the past years, it has been shown that the vascular endothelium lining the entire circulatory system can actively modulate the vascular tone and platelet functions by the release of autacoids, among them prostacyclin and endothelium-derived nitric oxide (EDRF). Recent experiments demonstrate that the release of EDRF is PO2-dependent, which suggests that endothelial cells may act as functional local oxygen sensors within the vascular system. 相似文献
1000.
Cloning defined regions of the human genome by microdissection of banded chromosomes and enzymatic amplification 总被引:48,自引:0,他引:48
The molecular analysis of many genetic diseases requires the isolation of probes for defined human chromosome regions. Existing techniques such as the screening of chromosome-specific libraries, subtractive DNA cloning and chromosome jumping are either tedious or not generally applicable. Microdissection and microcloning has successfully been applied to various chromosome regions in Drosophila and mouse, but conventional microtechniques are too coarse and inefficient for analysis of the human genome. Because microdissection has previously been used on unbanded chromosomes only, cell lines in which the chromosome of interest could be identified without banding had to be used. At least one hundred chromosomes were needed for dissection and lambda vectors used to achieve maximum cloning efficiency. Recombinant phage clones are, however, more difficult to characterize than plasmid clones. Here we describe the dissection of the Langer-Giedion syndrome region on chromosome 8 from GTG-banded metaphase chromosomes (G-banding with trypsin-Giemsa) and the universal enzymatic amplification of the dissected DNA. Eighty per cent of clones from this library (total yield 20,000) identify single-copy DNA sequences. Fifty per cent of clones detect deletions in two patients with Langer-Giedion syndrome. Although the other clones have not yet been mapped, this result demonstrates that thousands of region-specific probes can be isolated within ten days. 相似文献