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21.
A general approach to single-nucleotide polymorphism discovery 总被引:29,自引:0,他引:29
Marth GT Korf I Yandell MD Yeh RT Gu Z Zakeri H Stitziel NO Hillier L Kwok PY Gish WR 《Nature genetics》1999,23(4):452-456
Single-nucleotide polymorphisms (SNPs) are the most abundant form of human genetic variation and a resource for mapping complex genetic traits. The large volume of data produced by high-throughput sequencing projects is a rich and largely untapped source of SNPs (refs 2, 3, 4, 5). We present here a unified approach to the discovery of variations in genetic sequence data of arbitrary DNA sources. We propose to use the rapidly emerging genomic sequence as a template on which to layer often unmapped, fragmentary sequence data and to use base quality values to discern true allelic variations from sequencing errors. By taking advantage of the genomic sequence we are able to use simpler yet more accurate methods for sequence organization: fragment clustering, paralogue identification and multiple alignment. We analyse these sequences with a novel, Bayesian inference engine, POLYBAYES, to calculate the probability that a given site is polymorphic. Rigorous treatment of base quality permits completely automated evaluation of the full length of all sequences, without limitations on alignment depth. We demonstrate this approach by accurate SNP predictions in human ESTs aligned to finished and working-draft quality genomic sequences, a data set representative of the typical challenges of sequence-based SNP discovery. 相似文献
22.
23.
Inhibition of ice growth in supercooled solution by certain proteins is vital to the survival of many living organisms. Some fish, native to both subzero northern and southern waters, have special proteins or glycoproteins in their blood serum that inhibit ice formation. Whereas these proteins have only a very small effect on the melting temperature of ice, the temperature of these fish can fall to nearly 1 K below the melting point before ice crystals grow. This phenomenon is called freezing hysteresis, in contrast to the normal colligative effect of solutes that depresses the equilibrium temperature, around which small changes lead to crystal growth or melting depending on sign. Some insects also exhibit a serum freezing hysteresis. We report the effects of different degrees of supercooling on the habit and rates of growth of ice crystals from solutions of these antifreeze glycoproteins (AFGPs). We find that the crystallization rate is up to five times greater than that in pure water. 相似文献
24.
绒毛膜促性腺激素刺激对多囊卵巢综合征患者血管活性因子的影响 总被引:1,自引:1,他引:0
探讨促排卵治疗对多囊卵巢综合症(PCOS)患者血管活性因子血管紧张素-Ⅱ(AT-Ⅱ)、白介素-6(IL-6)、胰岛素样生长因子-1(IGF-1)的影响.21例PCOS患者与8例正常女性在自然或人工月经周期的第2 d卵泡期进行绒毛膜促性腺激素(HCG)促排卵,于试验前及试验后3、6、12、18、24 h静脉取血,放免法测定血清AT-ⅡI、L-6I、GF-1浓度.HCG刺激后PCOS组的血清AI-Ⅱ水平在各取血时点均升高,但只有3 h取血点是显著升高(P<0.05).PCOS组HCG刺激后各时点的血清AI-Ⅱ水平均高于对照组,也只有3 h取血点是显著高于对照组.血清IL-6及IGF-1水平在试验前后各时间点间差异均无显著性.结果提示HCG刺激促进PCOS患者外周血AT-Ⅱ水平升高. 相似文献
25.
Based on a large data base from 69 ionosonde stations distributed worldwide a comparative study is made on the global behavior
of ionospheric responses to three great magnetic storms occurring nearly at low and high activity phase of the 22nd solar
cycle. Depending on the season of storn occurrence, the global morphology of the ionospheric response to major magnetic storm
is very different. For the February 1986 storm, hemispheric asymmetry of storm effects is remarkable, and positive storm effects
are dominant in the winter hemisphere. Instead, for the two magnetic storms taking place near equinox in 1989, longlasting
decreases in Nm were observed in both hemispheres Large-scale TIDs propagating equatorward were seen during the main phases of the October
1989 magnetic storm at evening-night sector. On the other hand, short-lasting positive storm effects appearing as wave-like
disturbances in Nm were observed during the primary main phase of the 1986 storm in winter hemisphere. They seem to originate near the equatorial
region and travel polarward.
Supported by the National Natural Science Foundation of China and the Science Foundation of State Education Commitee of China
Xu Jisheng: born in Nov. 1946, Professor 相似文献
26.
Following the discovery by Kao and Hockman that ultra-low-loss optical fibres could be made from pure silica through the elimination of impurities, the ability to guide signals effectively at optical wavelengths has been assured. But there remains an important region of the spectrum--from 30 to 3,000 GHz (the millimetre-submillimetre band)--where low-loss waveguides are unknown. The main problem here in finding low-loss solids is no longer one of eliminating impurities, but is due to the presence of intrinsic vibration absorption bands. And the use of highly conducting materials is also precluded owing to high skin-depth losses in this part of the spectrum. Here we show that a combination of material and waveguide geometry can circumvent these difficulties. We adopt a ribbon-like structure with an aspect ratio of 10:1, fabricated from ceramic alumina (Coors' 998 Alumina), and the resulting waveguide has an attenuation factor of less than 10 dB km(-1) in the millimetre-submillimetre band. This attenuation is more than 100 times smaller than that of a typical ceramic (or other dielectric) circular rod waveguide and is sufficient for immediate application. 相似文献
27.
28.
Severe impairment of interleukin-1 and Toll-like receptor signalling in mice lacking IRAK-4 总被引:33,自引:0,他引:33
Suzuki N Suzuki S Duncan GS Millar DG Wada T Mirtsos C Takada H Wakeham A Itie A Li S Penninger JM Wesche H Ohashi PS Mak TW Yeh WC 《Nature》2002,416(6882):750-756
Toll-like receptors (TLRs), which recognize pathogen-associated molecular patterns, and members of the pro-inflammatory interleukin-1 receptor (IL-1R) family, share homologies in their cytoplasmic domains called Toll/IL-1R/plant R gene homology (TIR) domains. Intracellular signalling mechanisms mediated by TIRs are similar, with MyD88 (refs 5-8) and TRAF6 (refs 9, 10) having critical roles. Signal transduction between MyD88 and TRAF6 is known to involve the serine-threonine kinase IL-1 receptor-associated kinase 1 (IRAK-1) and two homologous proteins, IRAK-2 (ref. 12) and IRAK-M. However, the physiological functions of the IRAK molecules remain unclear, and gene-targeting studies have shown that IRAK-1 is only partially required for IL-1R and TLR signalling. Here we show by gene-targeting that IRAK-4, an IRAK molecule closely related to the Drosophila Pelle protein, is indispensable for the responses of animals and cultured cells to IL-1 and ligands that stimulate various TLRs. IRAK-4-deficient animals are completely resistant to a lethal dose of lipopolysaccharide (LPS). In addition, animals lacking IRAK-4 are severely impaired in their responses to viral and bacterial challenges. Our results indicate that IRAK-4 has an essential role in innate immunity. 相似文献
29.
Bianco PR Brewer LR Corzett M Balhorn R Yeh Y Kowalczykowski SC Baskin RJ 《Nature》2001,409(6818):374-378
RecBCD enzyme is a processive DNA helicase and nuclease that participates in the repair of chromosomal DNA through homologous recombination. We have visualized directly the movement of individual RecBCD enzymes on single molecules of double-stranded DNA (dsDNA). Detection involves the optical trapping of solitary, fluorescently tagged dsDNA molecules that are attached to polystyrene beads, and their visualization by fluorescence microscopy. Both helicase translocation and DNA unwinding are monitored by the displacement of fluorescent dye from the DNA by the enzyme. Here we show that unwinding is both continuous and processive, occurring at a maximum rate of 972 +/- 172 base pairs per second (0.30 microm s(-1)), with as many as 42,300 base pairs of dsDNA unwound by a single RecBCD enzyme molecule. The mean behaviour of the individual RecBCD enzyme molecules corresponds to that observed in bulk solution. 相似文献
30.
A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms 总被引:69,自引:0,他引:69
Sachidanandam R Weissman D Schmidt SC Kakol JM Stein LD Marth G Sherry S Mullikin JC Mortimore BJ Willey DL Hunt SE Cole CG Coggill PC Rice CM Ning Z Rogers J Bentley DR Kwok PY Mardis ER Yeh RT Schultz B Cook L Davenport R Dante M Fulton L Hillier L Waterston RH McPherson JD Gilman B Schaffner S Van Etten WJ Reich D Higgins J Daly MJ Blumenstiel B Baldwin J Stange-Thomann N Zody MC Linton L Lander ES Altshuler D;International SNP Map Working Group 《Nature》2001,409(6822):928-933
We describe a map of 1.42 million single nucleotide polymorphisms (SNPs) distributed throughout the human genome, providing an average density on available sequence of one SNP every 1.9 kilobases. These SNPs were primarily discovered by two projects: The SNP Consortium and the analysis of clone overlaps by the International Human Genome Sequencing Consortium. The map integrates all publicly available SNPs with described genes and other genomic features. We estimate that 60,000 SNPs fall within exon (coding and untranslated regions), and 85% of exons are within 5 kb of the nearest SNP. Nucleotide diversity varies greatly across the genome, in a manner broadly consistent with a standard population genetic model of human history. This high-density SNP map provides a public resource for defining haplotype variation across the genome, and should help to identify biomedically important genes for diagnosis and therapy. 相似文献