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961.
A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy 总被引:20,自引:0,他引:20
Zhang K Kniazeva M Han M Li W Yu Z Yang Z Li Y Metzker ML Allikmets R Zack DJ Kakuk LE Lagali PS Wong PW MacDonald IM Sieving PA Figueroa DJ Austin CP Gould RJ Ayyagari R Petrukhin K 《Nature genetics》2001,27(1):89-93
Stargardt-like macular dystrophy (STGD3, MIM 600110) and autosomal dominant macular dystrophy (adMD) are inherited forms of macular degeneration characterized by decreased visual acuity, macular atrophy and extensive fundus flecks. Genetic mapping data suggest that mutations in a single gene may be responsible for both conditions, already known to bear clinical resemblance. Here we limit the minimum genetic region for STGD3 and adMD to a 0.6-cM interval by recombination breakpoint mapping and identify a single 5-bp deletion within the protein-coding region of a new retinal photoreceptor-specific gene, ELOVL4, in all affected members of STGD3 and adMD families. Bioinformatic analysis of ELOVL4 revealed that it has homology to a group of yeast proteins that function in the biosynthesis of very long chain fatty acids. Our results are therefore the first to implicate the biosynthesis of fatty acids in the pathogenesis of inherited macular degeneration. 相似文献
962.
A radiation hybrid map of mouse genes 总被引:13,自引:0,他引:13
Hudson TJ Church DM Greenaway S Nguyen H Cook A Steen RG Van Etten WJ Castle AB Strivens MA Trickett P Heuston C Davison C Southwell A Hardisty R Varela-Carver A Haynes AR Rodriguez-Tome P Doi H Ko MS Pontius J Schriml L Wagner L Maglott D Brown SD Lander ES Schuler G Denny P 《Nature genetics》2001,29(2):201-205
A comprehensive gene-based map of a genome is a powerful tool for genetic studies and is especially useful for the positional cloning and positional candidate approaches. The availability of gene maps for multiple organisms provides the foundation for detailed conserved-orthology maps showing the correspondence between conserved genomic segments. These maps make it possible to use cross-species information in gene hunts and shed light on the evolutionary forces that shape the genome. Here we report a radiation hybrid map of mouse genes, a combined project of the Whitehead Institute/Massachusetts Institute of Technology Center for Genome Research, the Medical Research Council UK Mouse Genome Centre, and the National Center for Biotechnology Information. The map contains 11,109 genes, screened against the T31 RH panel and positioned relative to a reference map containing 2,280 mouse genetic markers. It includes 3,658 genes homologous to the human genome sequence and provides a framework for overlaying the human genome sequence to the mouse and for sequencing the mouse genome. 相似文献
963.
964.
The different expression patterns of genes for uncoupling proteins (UCPs) 1, 2 and 3 (ucp1, ucp2 and ucp3) were studied in interscapular brown adipose tissue (BAT) and in four white adipose tissue (WAT) depots (epididymal, inguinal, mesenteric and retroperitoneal) in male rats of different ages (18 days-12 months). UCP mRNA expression levels were determined by Northern blotting. In BAT, there were high levels of expression of UCP1 and UCP3 mRNA, but no detectable levels of UCP2 mRNA. Both ucp1 and ucp3 followed a similar expression pattern with age, with high levels in suckling rats which decreased to 50% or less in rats just under 2 months old, declining thereafter until 5 months and then recovering with age. However, an additional peak of expression was observed for ucp3 at the age of 3 months. In WAT, ucp1 expression was rare: occasional expression was found for UCP1 mRNA in the retroperitoneal depot in suckling rats and in the epididymal and inguinal depots in suckling and mature adult rats. ucp2 and ucp3 had different developmental expression patterns, but these were similar for each gene in the different depots studied. UCP3 mRNA was highly expressed in rats soon after birth, it decreased until 3 months, and increased thereafter, except for the mesenteric WAT where ucp3 expression decreased until 7 months before recovering. The fact that changes with age of both ucp1 and ucp3 expression have a similar profile in BAT, which is also similar to the ucp3 and also ucp1 profiles in some WAT depots, might reflect a common regulatory pattern for the expression of these genes, and also a common function. In contrast to ucp1 and ucp3, ucp2 had a peak of expression at about 2 months, and lower expression at 3 months, suggesting different regulation and probably a different role for this UCP. 相似文献
965.
966.
Pfeifer GP 《Nature genetics》2001,28(1):3-4
Certain human cancers and carcinogen-induced rodent tumors commonly contain Kras2 mutations. This activated form of ras has always been described as a dominant oncogene. A new study indicates that wildtype Kras2 has properties of a tumor suppressor gene and may have the capacity to reduce the transforming potential of oncogenically activated ras. 相似文献
967.
An abundance of X-linked genes expressed in spermatogonia 总被引:22,自引:0,他引:22
Spermatogonia are the self-renewing, mitotic germ cells of the testis from which sperm arise by means of the differentiation pathway known as spermatogenesis. By contrast with hematopoietic and other mammalian stem-cell populations, which have been subjects of intense molecular genetic investigation, spermatogonia have remained largely unexplored at the molecular level. Here we describe a systematic search for genes expressed in mouse spermatogonia, but not in somatic tissues. We identified 25 genes (19 of which are novel) that are expressed in only male germ cells. Of the 25 genes, 3 are Y-linked and 10 are X-linked. If these genes had been distributed randomly in the genome, one would have expected zero to two of the genes to be X-linked. Our findings indicate that the X chromosome has a predominant role in pre-meiotic stages of mammalian spermatogenesis. We hypothesize that the X chromosome acquired this prominent role in male germ-cell development as it evolved from an ordinary, unspecialized autosome. 相似文献
968.
Marth G Yeh R Minton M Donaldson R Li Q Duan S Davenport R Miller RD Kwok PY 《Nature genetics》2001,27(4):371-372
There is a concerted effort by a number of public and private groups to identify a large set of human single-nucleotide polymorphisms (SNPs). As of March 2001, 2.84 million SNPs have been deposited in the public database, dbSNP, at the National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov/SNP/). The 2.84 million SNPs can be grouped into 1.65 million non-redundant SNPs. As part of the International SNP Map Working Group, we recently published a high-density SNP map of the human genome consisting of 1.42 million SNPs (ref. 3). In addition, numerous SNPs are maintained in proprietary databases. Our survey of more than 1,200 SNPs indicates that more than 80% of TSC and Washington University candidate SNPs are polymorphic and that approximately 50% of the candidate SNPs from these two sources are common SNPs (with minor allele frequency of > or =20%) in any given population. 相似文献
969.
Grimm DR Colter MB Braunschweig M Alexander LJ Neame PJ Kim HK 《Cellular and molecular life sciences : CMLS》2001,58(1):148-159
Factor V is a plasma protein essential for blood coagulation. This protein is involved in activated protein C resistance,
the most common inherited thrombotic disorder known. We utilized the polymerase chain reaction to clone the porcine factor
V gene by generating overlapping clones amplified with primers chosen by comparison with known nucleotide sequences. The porcine
factor V cDNA contig encodes a predicted 2258-amino acid protein, making it the largest in comparison to the bovine, human,
and murine proteins. Porcine factor V has the highest level of homology with bovine factor V, but also has high levels of
conservation of important residues with all the species. Radiation hybrid mapping assigned the porcine factor V gene to chromosome
4. Three-dimensional models of factor V were generated and used to analyze membrane-binding sites in terms of conserved, and
therefore likely important residues.
Received 3 October 2000; revised 23 November 2000; accepted 6 December 2000 相似文献
970.
Larbalestier DC Cooley LD Rikel MO Polyanskii AA Jiang J Patnaik S Cai XY Feldmann DM Gurevich A Squitieri AA Naus MT Eom CB Hellstrom EE Cava RJ Regan KA Rogado N Hayward MA He T Slusky JS Khalifah P Inumaru K Haas M 《Nature》2001,410(6825):186-189
The discovery of superconductivity at 39 K in magnesium diboride, MgB2, raises many issues, a critical one being whether this material resembles a high-temperature copper oxide superconductor or a low-temperature metallic superconductor in terms of its behaviour in strong magnetic fields. Although the copper oxides exhibit very high transition temperatures, their in-field performance is compromized by their large anisotropy, the result of which is to restrict high bulk current densities to a region much less than the full magnetic-field-temperature (H-T) space over which superconductivity is found. Moreover, the weak coupling across grain boundaries makes transport current densities in untextured polycrystalline samples low and strongly sensitive to magnetic field. Here we report that, despite the multiphase, untextured, microscale, subdivided nature of our MgB2 samples, supercurrents flow throughout the material without exhibiting strong sensitivity to weak magnetic fields. Our combined magnetization, magneto-optical, microscopy and X-ray investigations show that the supercurrent density is mostly determined by flux pinning, rather than by the grain boundary connectivity. Our results therefore suggest that this new superconductor class is not compromized by weak-link problems, a conclusion of significance for practical applications if higher temperature analogues of this compound can be discovered. 相似文献