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71.
Systematic generation of high-resolution deletion coverage of the Drosophila melanogaster genome 总被引:1,自引:0,他引:1
Parks AL Cook KR Belvin M Dompe NA Fawcett R Huppert K Tan LR Winter CG Bogart KP Deal JE Deal-Herr ME Grant D Marcinko M Miyazaki WY Robertson S Shaw KJ Tabios M Vysotskaia V Zhao L Andrade RS Edgar KA Howie E Killpack K Milash B Norton A Thao D Whittaker K Winner MA Friedman L Margolis J Singer MA Kopczynski C Curtis D Kaufman TC Plowman GD Duyk G Francis-Lang HL 《Nature genetics》2004,36(3):288-292
In fruit fly research, chromosomal deletions are indispensable tools for mapping mutations, characterizing alleles and identifying interacting loci. Most widely used deletions were generated by irradiation or chemical mutagenesis. These methods are labor-intensive, generate random breakpoints and result in unwanted secondary mutations that can confound phenotypic analyses. Most of the existing deletions are large, have molecularly undefined endpoints and are maintained in genetically complex stocks. Furthermore, the existence of haplolethal or haplosterile loci makes the recovery of deletions of certain regions exceedingly difficult by traditional methods, resulting in gaps in coverage. Here we describe two methods that address these problems by providing for the systematic isolation of targeted deletions in the D. melanogaster genome. The first strategy used a P element-based technique to generate deletions that closely flank haploinsufficient genes and minimize undeleted regions. This deletion set has increased overall genomic coverage by 5-7%. The second strategy used FLP recombinase and the large array of FRT-bearing insertions described in the accompanying paper to generate 519 isogenic deletions with molecularly defined endpoints. This second deletion collection provides 56% genome coverage so far. The latter methodology enables the generation of small custom deletions with predictable endpoints throughout the genome and should make their isolation a simple and routine task. 相似文献
72.
Perennial water ice identified in the south polar cap of Mars 总被引:1,自引:0,他引:1
Bibring JP Langevin Y Poulet F Gendrin A Gondet B Berthé M Soufflot A Drossart P Combes M Bellucci G Moroz V Mangold N Schmitt B;OMEGA Team 《Nature》2004,428(6983):627-630
The inventory of water and carbon dioxide reservoirs on Mars are important clues for understanding the geological, climatic and potentially exobiological evolution of the planet. From the early mapping observation of the permanent ice caps on the martian poles, the northern cap was believed to be mainly composed of water ice, whereas the southern cap was thought to be constituted of carbon dioxide ice. However, recent missions (NASA missions Mars Global Surveyor and Odyssey) have revealed surface structures, altimetry profiles, underlying buried hydrogen, and temperatures of the south polar regions that are thermodynamically consistent with a mixture of surface water ice and carbon dioxide. Here we present the first direct identification and mapping of both carbon dioxide and water ice in the martian high southern latitudes, at a resolution of 2 km, during the local summer, when the extent of the polar ice is at its minimum. We observe that this south polar cap contains perennial water ice in extended areas: as a small admixture to carbon dioxide in the bright regions; associated with dust, without carbon dioxide, at the edges of this bright cap; and, unexpectedly, in large areas tens of kilometres away from the bright cap. 相似文献
73.
Reboul J Vaglio P Rual JF Lamesch P Martinez M Armstrong CM Li S Jacotot L Bertin N Janky R Moore T Hudson JR Hartley JL Brasch MA Vandenhaute J Boulton S Endress GA Jenna S Chevet E Papasotiropoulos V Tolias PP Ptacek J Snyder M Huang R Chance MR Lee H Doucette-Stamm L Hill DE Vidal M 《Nature genetics》2003,34(1):35-41
To verify the genome annotation and to create a resource to functionally characterize the proteome, we attempted to Gateway-clone all predicted protein-encoding open reading frames (ORFs), or the 'ORFeome,' of Caenorhabditis elegans. We successfully cloned approximately 12,000 ORFs (ORFeome 1.1), of which roughly 4,000 correspond to genes that are untouched by any cDNA or expressed-sequence tag (EST). More than 50% of predicted genes needed corrections in their intron-exon structures. Notably, approximately 11,000 C. elegans proteins can now be expressed under many conditions and characterized using various high-throughput strategies, including large-scale interactome mapping. We suggest that similar ORFeome projects will be valuable for other organisms, including humans. 相似文献
74.
Allen M Heinzmann A Noguchi E Abecasis G Broxholme J Ponting CP Bhattacharyya S Tinsley J Zhang Y Holt R Jones EY Lench N Carey A Jones H Dickens NJ Dimon C Nicholls R Baker C Xue L Townsend E Kabesch M Weiland SK Carr D von Mutius E Adcock IM Barnes PJ Lathrop GM Edwards M Moffatt MF Cookson WO 《Nature genetics》2003,35(3):258-263
Asthma is a common disease in children and young adults. Four separate reports have linked asthma and related phenotypes to an ill-defined interval between 2q14 and 2q32 (refs. 1-4), and two mouse genome screens have linked bronchial hyper-responsiveness to the region homologous to 2q14 (refs. 5,6). We found and replicated association between asthma and the D2S308 microsatellite, 800 kb distal to the IL1 cluster on 2q14. We sequenced the surrounding region and constructed a comprehensive, high-density, single-nucleotide polymorphism (SNP) linkage disequilibrium (LD) map. SNP association was limited to the initial exons of a solitary gene of 3.6 kb (DPP10), which extends over 1 Mb of genomic DNA. DPP10 encodes a homolog of dipeptidyl peptidases (DPPs) that cleave terminal dipeptides from cytokines and chemokines, and it presents a potential new target for asthma therapy. 相似文献
75.
Classifications are generally pictured in the form of hierarchical trees, also called dendrograms. A dendrogram is the graphical
representation of an ultrametric (=cophenetic) matrix; so dendrograms can be compared to one another by comparing their cophenetic
matrices. Three methods used in testing the correlation between matrices corresponding to dendrograms are evaluated. The three
permutational procedures make use of different aspects of the information to compare dendrograms: the Mantel procedure permutes
label positions only; the binary tree methods randomize the topology as well; the double-permutation procedure is based on
all the information included in a dendrogram, that is: topology, label positions, and cluster heights. Theoretical and empirical
investigations of these methods are carried out to evaluate their relative performance. Simulations show that the Mantel test
is too conservative when applied to the comparison of dendrograms; the methods of binary tree comparisons do slightly better;
only the doublepermutation test provides unbiased type I error.
Les arbres utilisés pour illustrés les groupements sont généralement représentés sous la forme de classifications hiérarchiques
ou dendrogrammes. Un dendrogramme représente graphiquement l’information contenue dans la matrice ultramétrique (=cophénétique)
correspondant à la classification. Dès ultramétriques correspondantes. Nous comparons trois méthodes permettant d’évaluer
la signification statistique du coefficient de correlation mesuré entre deux matrices ultramétriques. Ces trois tests par
permutations tiennent compte d’aspects différents pour comparer des dendrogrammes: le test de Mantel permute les feuilles
de l’arbre, les méthodes pour arbres binaires permutent les feuilles et la topologie, alors que la procédure à double permutation
permute les feuilles, la topologie et les niveaux de fusion des dendrogrammes comparés. L’efficacité relative des trois méthodes
est évaluée empiriquement et théoriquement. Nos résultats suggèrent l’utilisation préférentielle du test à double permutation
pour la comparaison de dendrogrammes: le test de Mantel s’avère trop conservateur, tandis que les méthodes pour arbres binaires
ne sont pas toujours adéquates.
This work was supported by NSERC grant no. A7738 to Pierre Legendre and by a NSERC scholarship to F.-J. Lapointe. 相似文献
This work was supported by NSERC grant no. A7738 to Pierre Legendre and by a NSERC scholarship to F.-J. Lapointe. 相似文献
76.
Summary Condensed chromatin shows globules of 300 Å formed by 8 to 10 nucleosomes. Each globule might be an uncoiled turn of a supercoil. This supercoil forms major coils along the fibre.This work was supported by grants from Brazilian CNPq, FAPESP and FEDIB.We thank Dr A. Brunner Jr for the permission to use the electron microscope. 相似文献
77.
Melita Tajić M. Gerenčer A. Kaštelan 《Cellular and molecular life sciences : CMLS》1981,37(4):427-429
Summary The concentration of plasma testosterone (T) and dihydrotestosterone (DHT) was determined in 2 groups of nonpregnant and pregnant women. The 1st group consisted of normal women and the 2nd of women with recurrent pregnancy disorders of unknown etiology. Significantly higher concentration of plasma DHT in nonpregnant women from the 2nd group was found (44.9±22 ng/100 ml) as compared to nonpregnant normals (24.2±5.2 ng/100 ml), p<0.01. There was no difference in the concentration of plasma T between the groups studied (p=0.165).Acknowledgment. The authors thank Prof. A. Draani, Mrs Lj. Vukeli and Mrs Z. Tomakovi for their collaboration in this study. This study was supported by the Scientific Fund of SR Croatia (Zagreb), SIZ V. 相似文献
78.
Pujana MA Han JD Starita LM Stevens KN Tewari M Ahn JS Rennert G Moreno V Kirchhoff T Gold B Assmann V Elshamy WM Rual JF Levine D Rozek LS Gelman RS Gunsalus KC Greenberg RA Sobhian B Bertin N Venkatesan K Ayivi-Guedehoussou N Solé X Hernández P Lázaro C Nathanson KL Weber BL Cusick ME Hill DE Offit K Livingston DM Gruber SB Parvin JD Vidal M 《Nature genetics》2007,39(11):1338-1349
Many cancer-associated genes remain to be identified to clarify the underlying molecular mechanisms of cancer susceptibility and progression. Better understanding is also required of how mutations in cancer genes affect their products in the context of complex cellular networks. Here we have used a network modeling strategy to identify genes potentially associated with higher risk of breast cancer. Starting with four known genes encoding tumor suppressors of breast cancer, we combined gene expression profiling with functional genomic and proteomic (or 'omic') data from various species to generate a network containing 118 genes linked by 866 potential functional associations. This network shows higher connectivity than expected by chance, suggesting that its components function in biologically related pathways. One of the components of the network is HMMR, encoding a centrosome subunit, for which we demonstrate previously unknown functional associations with the breast cancer-associated gene BRCA1. Two case-control studies of incident breast cancer indicate that the HMMR locus is associated with higher risk of breast cancer in humans. Our network modeling strategy should be useful for the discovery of additional cancer-associated genes. 相似文献
79.
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
80.
Zanke BW Greenwood CM Rangrej J Kustra R Tenesa A Farrington SM Prendergast J Olschwang S Chiang T Crowdy E Ferretti V Laflamme P Sundararajan S Roumy S Olivier JF Robidoux F Sladek R Montpetit A Campbell P Bezieau S O'Shea AM Zogopoulos G Cotterchio M Newcomb P McLaughlin J Younghusband B Green R Green J Porteous ME Campbell H Blanche H Sahbatou M Tubacher E Bonaiti-Pellié C Buecher B Riboli E Kury S Chanock SJ Potter J Thomas G Gallinger S Hudson TJ Dunlop MG 《Nature genetics》2007,39(8):989-994
Using a multistage genetic association approach comprising 7,480 affected individuals and 7,779 controls, we identified markers in chromosomal region 8q24 associated with colorectal cancer. In stage 1, we genotyped 99,632 SNPs in 1,257 affected individuals and 1,336 controls from Ontario. In stages 2-4, we performed serial replication studies using 4,024 affected individuals and 4,042 controls from Seattle, Newfoundland and Scotland. We identified one locus on chromosome 8q24 and another on 9p24 having combined odds ratios (OR) for stages 1-4 of 1.18 (trend; P = 1.41 x 10(-8)) and 1.14 (trend; P = 1.32 x 10(-5)), respectively. Additional analyses in 2,199 affected individuals and 2,401 controls from France and Europe supported the association at the 8q24 locus (OR = 1.16, trend; 95% confidence interval (c.i.): 1.07-1.26; P = 5.05 x 10(-4)). A summary across all seven studies at the 8q24 locus was highly significant (OR = 1.17, c.i.: 1.12-1.23; P = 3.16 x 10(-11)). This locus has also been implicated in prostate cancer. 相似文献