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排序方式: 共有251条查询结果,搜索用时 76 毫秒
201.
Turnbull C Perdeaux ER Pernet D Naranjo A Renwick A Seal S Munoz-Xicola RM Hanks S Slade I Zachariou A Warren-Perry M Ruark E Gerrard M Hale J Hewitt M Kohler J Lane S Levitt G Madi M Morland B Neefjes V Nicholdson J Picton S Pizer B Ronghe M Stevens M Traunecker H Stiller CA Pritchard-Jones K Dome J Grundy P Rahman N 《Nature genetics》2012,44(6):681-684
Wilms tumor is the most common renal malignancy of childhood. To identify common variants that confer susceptibility to Wilms tumor, we conducted a genome-wide association study in 757 individuals with Wilms tumor (cases) and 1,879 controls. We evaluated ten SNPs in regions significantly associated at P < 5 × 10(-5) in two independent replication series from the UK (769 cases and 2,814 controls) and the United States (719 cases and 1,037 controls). We identified clear significant associations at 2p24 (rs3755132, P = 1.03 × 10(-14); rs807624, P = 1.32 × 10(-14)) and 11q14 (rs790356, P = 4.25 × 10(-15)). Both regions contain genes that are plausibly related to Wilms tumorigenesis. We also identified candidate association signals at 5q14, 22q12 and Xp22. 相似文献
202.
We report the discovery in Utah of Dipodomys spectabilis, a species previously unknown to occur in the state. We searched for D. spectabilis in extreme southeastern Utah, south of the San Juan River, and were successful in finding mounds and burrows characteristic of the species and in capturing one individual. This is the northernmost record for D. spectabilis and extends its known range ~84 km northwest of the nearest previously reported locality (Fruitland, San Juan County, New Mexico). A flea, Meringis rectus, collected from D. spectabilis, is also the first record of its species in Utah. Reportamos el descubrimiento en Utah de Dipodomys spectabilis, una especie cuya presencia en el estado no había sido observada previamente. Buscamos D. spectabilis en el extremo sureste de Utah, al sur del Río San Juan, y logramos encontrar montículos y túneles típicos de esta especie y capturar un espécimen. Este es el registro más al norte para D. spectabilis y se extiende su rango de distribución conocida a ~84 km al noroeste de la localidad más cercana previamente reportada (Fruitland, condado de San Juan, Nuevo Mexico). Es también el primer registro en Utah para Meringis rectus, una pulga recolectada en D. spectabilis. 相似文献
203.
Wang K Kan J Yuen ST Shi ST Chu KM Law S Chan TL Kan Z Chan AS Tsui WY Lee SP Ho SL Chan AK Cheng GH Roberts PC Rejto PA Gibson NW Pocalyko DJ Mao M Xu J Leung SY 《Nature genetics》2011,43(12):1219-1223
Gastric cancer is a heterogeneous disease with multiple environmental etiologies and alternative pathways of carcinogenesis. Beyond mutations in TP53, alterations in other genes or pathways account for only small subsets of the disease. We performed exome sequencing of 22 gastric cancer samples and identified previously unreported mutated genes and pathway alterations; in particular, we found genes involved in chromatin modification to be commonly mutated. A downstream validation study confirmed frequent inactivating mutations or protein deficiency of ARID1A, which encodes a member of the SWI-SNF chromatin remodeling family, in 83% of gastric cancers with microsatellite instability (MSI), 73% of those with Epstein-Barr virus (EBV) infection and 11% of those that were not infected with EBV and microsatellite stable (MSS). The mutation spectrum for ARID1A differs between molecular subtypes of gastric cancer, and mutation prevalence is negatively associated with mutations in TP53. Clinically, ARID1A alterations were associated with better prognosis in a stage-independent manner. These results reveal the genomic landscape, and highlight the importance of chromatin remodeling, in the molecular taxonomy of gastric cancer. 相似文献
204.
Schunkert H König IR Kathiresan S Reilly MP Assimes TL Holm H Preuss M Stewart AF Barbalic M Gieger C Absher D Aherrahrou Z Allayee H Altshuler D Anand SS Andersen K Anderson JL Ardissino D Ball SG Balmforth AJ Barnes TA Becker DM Becker LC Berger K Bis JC Boekholdt SM Boerwinkle E Braund PS Brown MJ Burnett MS Buysschaert I;Cardiogenics Carlquist JF Chen L Cichon S Codd V Davies RW Dedoussis G Dehghan A Demissie S Devaney JM Diemert P Do R Doering A Eifert S Mokhtari NE Ellis SG Elosua R 《Nature genetics》2011,43(4):333-338
We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 × 10?? and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits. 相似文献
205.
March HN Rust AG Wright NA ten Hoeve J de Ridder J Eldridge M van der Weyden L Berns A Gadiot J Uren A Kemp R Arends MJ Wessels LF Winton DJ Adams DJ 《Nature genetics》2011,43(12):1202-1209
The evolution of colorectal cancer suggests the involvement of many genes. To identify new drivers of intestinal cancer, we performed insertional mutagenesis using the Sleeping Beauty transposon system in mice carrying germline or somatic Apc mutations. By analyzing common insertion sites (CISs) isolated from 446 tumors, we identified many hundreds of candidate cancer drivers. Comparison to human data sets suggested that 234 CIS-targeted genes are also dysregulated in human colorectal cancers. In addition, we found 183 CIS-containing genes that are candidate Wnt targets and showed that 20 CISs-containing genes are newly discovered modifiers of canonical Wnt signaling. We also identified mutations associated with a subset of tumors containing an expanded number of Paneth cells, a hallmark of deregulated Wnt signaling, and genes associated with more severe dysplasia included those encoding members of the FGF signaling cascade. Some 70 genes had co-occurrence of CIS pairs, clustering into 38 sub-networks that may regulate tumor development. 相似文献
206.
In 1983 zinc phosphide, strychnine with prebait, and strychnine without prebait were applied to black-tailed prairie dog ( Cynomys ludovicianus ) colonies in west central South Dakota. Short-term (four days later) and long-term (one year later) impacts of the rodenticides on Horned Larks ( Eremophila alpestris ) and other granivorous birds inhabiting prairie dog colonies were evaluated. Hrned Larks and 49 other bird species were observed. Immediate impacts reduced Horned Lark relative densities 66% with strychnine only and 55% with prebaited strychnine. Zinc phosphide caused no measurable reduction. Horned Larks showed no long-term direct impacts. Indirect negative impacts occurred through habitat changes following prairie dog control. The granivorous guild showed no short- or long-term effects. 相似文献
207.
Barton A Thomson W Ke X Eyre S Hinks A Bowes J Plant D Gibbons LJ;Wellcome Trust Case Control Consortium;YEAR Consortium;BIRAC Consortium Wilson AG Bax DE Morgan AW Emery P Steer S Hocking L Reid DM Wordsworth P Harrison P Worthington J 《Nature genetics》2008,40(10):1156-1159
The WTCCC study identified 49 SNPs putatively associated with rheumatoid arthritis at P = 1 x 10(-4) - 1 x 10(-5) (tier 3). Here we show that three of these SNPs, mapping to chromosome 10p15 (rs4750316), 12q13 (rs1678542) and 22q13 (rs3218253), are also associated (trend P = 4 x 10(-5), P = 4 x 10(-4) and P = 4 x 10(-4), respectively) in a validation study of 4,106 individuals with rheumatoid arthritis and an expanded reference group of 11,238 subjects, confirming them as true susceptibility loci in individuals of European ancestry. 相似文献
208.
Broderick P Chubb D Johnson DC Weinhold N Försti A Lloyd A Olver B Ma YP Dobbins SE Walker BA Davies FE Gregory WA Child JA Ross FM Jackson GH Neben K Jauch A Hoffmann P Mühleisen TW Nöthen MM Moebus S Tomlinson IP Goldschmidt H Hemminki K Morgan GJ Houlston RS 《Nature genetics》2012,44(1):58-61
To identify risk variants for multiple myeloma, we conducted a genome-wide association study of 1,675 individuals with multiple myeloma and 5,903 control subjects. We identified risk loci for multiple myeloma at 3p22.1 (rs1052501 in ULK4; odds ratio (OR) = 1.32; P = 7.47 × 10(-9)) and 7p15.3 (rs4487645, OR = 1.38; P = 3.33 × 10(-15)). In addition, we observed a promising association at 2p23.3 (rs6746082, OR = 1.29; P = 1.22 × 10(-7)). Our study identifies new genomic regions associated with multiple myeloma risk that may lead to new etiological insights. 相似文献
209.
Daniel W. Lambert Nicola E. Clarke Anthony J. Turner 《Cellular and molecular life sciences : CMLS》2010,67(1):89-98
The renin-angiotensin system (RAS) is a critical regulator of blood pressure and fluid homeostasis. Angiotensin II, the primary
bioactive peptide of the RAS, is generated from angiotensin I by angiotensin-converting enzyme (ACE). A homologue of ACE,
ACE2, is able to convert angiotensin II to a peptide with opposing effects, angiotensin-(1-7). It is proposed that disturbance
of the balance of ACE and ACE2 expression and/or function is important in pathologies in which angiotensin II plays a role.
These include cardiovascular and renal disease, lung injury and liver fibrosis. The critical roles of ACE and ACE2 in regulating
angiotensin II levels have traditionally focussed attention on their activities as angiotensinases. Recent discoveries, however,
have illuminated the roles of these enzymes and of the ACE2 homologue, collectrin, in intracellular trafficking and signalling.
This paper reviews the key literature regarding both the catalytic and non-catalytic roles of the angiotensin-converting enzyme
gene family. 相似文献
210.
Kras is the most frequently mutated ras family member in lung carcinomas, whereas Hras mutations are common in tumors from stratified epithelia such as the skin. Using a Hras knock-in mouse model, we demonstrate that specificity for Kras mutations in lung and Hras mutations in skin tumors is determined by local regulatory elements in the target ras genes. Although the Kras 4A isoform is dispensable for mouse development, it is the most important isoform for lung carcinogenesis in vivo and for the inhibitory effect of wild-type (WT) Kras on the mutant allele. Kras 4A expression is detected in a subpopulation of normal lung epithelial cells, but at very low levels in lung tumors, suggesting that it may not be required for tumor progression. The two Kras isoforms undergo different post-translational modifications; therefore, these findings can have implications for the design of therapeutic strategies for inhibiting oncogenic Kras activity in human cancers. 相似文献