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41.
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
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提出了一种能够提高ITU-TG.729算法性能的静音检测技术,该技术的引入不仅可以降低G.729的语音通讯平均传输出特率,而且可以大量节省G.729压缩和解压过程的实际运算量,通过在不同的噪声背景下的性能分析,该静音检测技术的引入不会对G.729算法的合成语音质量产生明显的影响。 相似文献
44.
This part demonstrates a prototype system which has been constructed to enable the allocation of orders of different product types to different manufacturing locations . ' What - if' experiments using this system show that different allocation rules would provide different outcomes in terms of the number of unallocated orders. A high number of unallocated orders will have a direct Impact on workload. Further research effort is necessary to channel into the exercbe of production order allocation with particular reference to allocation rules. 相似文献
45.
Chung RS Fung SJ Leung YK Walker AK McCormack GH Chuah MI Vickers JC West AK 《Cellular and molecular life sciences : CMLS》2007,64(19-20):2716-2722
Metallothionein (MT) expression is rapidly up-regulated following CNS injury, and there is a strong correlation between the presence or absence of MTand improved or impaired (respectively) recovery from such trauma.We now report that a distinct subset of NG2-positive, GFAP-negative glial cells bordering the injury tract express MT following focal injury to the adult rat neocortex. To confirm the ability of these NG2 glial cells to express MT, we have isolated and cultured them and identified that they can express MT following stimulation with zinc. To investigate the functional importance of MT expression by NG2 glial cells, we plated cortical neurons onto these cells and found that expression of MT enhanced the permissivity of NG2 glial cells to neurite outgrowth. Our data suggest that expression of MT by NG2 glial cells may contribute to the overall permissiveness of these cells to axon regeneration. 相似文献
46.
Abecasis G Tam PK Bustamante CD Ostrander EA Scherer SW Chanock SJ Kwok PY Brookes AJ 《Nature genetics》2007,39(2):153-155
The eighth annual Human Genome Variation Meeting was held in September 2006 in the Hong Kong Special Administrative Region, China. The meeting highlighted recent advances in characterization of genetic variation, including genome-wide association studies and structural variation. 相似文献
47.
Todd JA Walker NM Cooper JD Smyth DJ Downes K Plagnol V Bailey R Nejentsev S Field SF Payne F Lowe CE Szeszko JS Hafler JP Zeitels L Yang JH Vella A Nutland S Stevens HE Schuilenburg H Coleman G Maisuria M Meadows W Smink LJ Healy B Burren OS Lam AA Ovington NR Allen J Adlem E Leung HT Wallace C Howson JM Guja C Ionescu-Tîrgovişte C;Genetics of Type Diabetes in Finland Simmonds MJ Heward JM Gough SC;Wellcome Trust Case Control Consortium Dunger DB Wicker LS Clayton DG 《Nature genetics》2007,39(7):857-864
The Wellcome Trust Case Control Consortium (WTCCC) primary genome-wide association (GWA) scan on seven diseases, including the multifactorial autoimmune disease type 1 diabetes (T1D), shows associations at P < 5 x 10(-7) between T1D and six chromosome regions: 12q24, 12q13, 16p13, 18p11, 12p13 and 4q27. Here, we attempted to validate these and six other top findings in 4,000 individuals with T1D, 5,000 controls and 2,997 family trios independent of the WTCCC study. We confirmed unequivocally the associations of 12q24, 12q13, 16p13 and 18p11 (P(follow-up) 相似文献
48.
Cotton RG; Human Variome Project Appelbe W Auerbach AD Becker K Bodmer W Boone DJ Boulyjenkov V Brahmachari S Brody L Brookes A Brown AF Byers P Cantu JM Cassiman JJ Claustres M Concannon P Cotton RG den Dunnen JT Flicek P Gibbs R Hall J Hasler J Katz M Kwok PY Laradi S Lindblom A Maglott D Marsh S Masimirembwa CM Minoshima S de Ramirez AM Pagon R Ramesar R Ravine D Richards S Rimoin D Ring HZ Scriver CR Sherry S Shimizu N Stein L Tadmouri GO Taylor G Watson M 《Nature genetics》2007,39(4):433-436
Lists of variations in genomic DNA and their effects have been kept for some time and have been used in diagnostics and research. Although these lists have been carefully gathered and curated, there has been little standardization and coordination, complicating their use. Given the myriad possible variations in the estimated 24,000 genes in the human genome, it would be useful to have standard criteria for databases of variation. Incomplete collection and ascertainment of variants demonstrates a need for a universally accessible system. These and other problems led to the World Heath Organization-cosponsored meeting on June 20-23, 2006 in Melbourne, Australia, which launched the Human Variome Project. This meeting addressed all areas of human genetics relevant to collection of information on variation and its effects. Members of each of eight sessions (the clinic and phenotype, the diagnostic laboratory, the research laboratory, curation and collection, informatics, relevance to the emerging world, integration and federation and funding and sustainability) developed a number of recommendations that were then organized into a total of 96 recommendations to act as a foundation for future work worldwide. Here we summarize the background of the project, the meeting and its recommendations. 相似文献
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50.
In hyperalgesic states, observed commonly as a major symptom of tissue inflammation or after central or peripheral nerve injury, non-noxious stimuli produce pain and noxious stimuli are perceived as more painful than usual. The mechanisms underlying the generation of hyperalgesia are not known. In patients with causalgia (burning pain and severe hyperalgesia after a nerve injury) activation of sympathetic post-ganglionic neurones or application of noradrenaline to painful skin exacerbates pain and hyperalgesia while sympathectomy may afford complete relief. One suggestion is that noradrenaline released from sympathetic post-ganglionic neurons increases the discharge of damaged small-diameter afferents by a direct action on the primary afferents. Here we present a new model for noradrenaline-sensitive hyperalgesia and demonstrate that the site of action of noradrenaline is not on the primary afferents but rather is presynaptic on the sympathetic post-ganglionic terminals. 相似文献