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1.
We performed a genome-wide association study of melanoma in a discovery cohort of 2,168 Australian individuals with melanoma and 4,387 control individuals. In this discovery phase, we confirm several previously characterized melanoma-associated loci at MC1R, ASIP and MTAP-CDKN2A. We selected variants at nine loci for replication in three independent case-control studies (Europe: 2,804 subjects with melanoma, 7,618 control subjects; United States 1: 1,804 subjects with melanoma, 1,026 control subjects; United States 2: 585 subjects with melanoma, 6,500 control subjects). The combined meta-analysis of all case-control studies identified a new susceptibility locus at 1q21.3 (rs7412746, P = 9.0 × 10(-11), OR in combined replication cohorts of 0.89 (95% CI 0.85-0.95)). We also show evidence suggesting that melanoma associates with 1q42.12 (rs3219090, P = 9.3 × 10(-8)). The associated variants at the 1q21.3 locus span a region with ten genes, and plausible candidate genes for melanoma susceptibility include ARNT and SETDB1. Variants at the 1q21.3 locus do not seem to be associated with human pigmentation or measures of nevus density.  相似文献   
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We report a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 individuals with severe visual field loss (cases) and 3,956 controls. We identified associated loci at TMCO1 (rs4656461[G] odds ratio (OR) = 1.68, P = 6.1 × 10(-10)) and CDKN2B-AS1 (rs4977756[A] OR = 1.50, P = 4.7 × 10(-9)). We replicated these associations in an independent cohort of cases with advanced OAG (rs4656461 P = 0.010; rs4977756 P = 0.042) and two additional cohorts of less severe OAG (rs4656461 combined discovery and replication P = 6.00 × 10(-14), OR = 1.51, 95% CI 1.35-1.68; rs4977756 combined P = 1.35 × 10(-14), OR = 1.39, 95% CI 1.28-1.51). We show retinal expression of genes at both loci in human ocular tissues. We also show that CDKN2A and CDKN2B are upregulated in the retina of a rat model of glaucoma.  相似文献   
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Summary Divalent metal ions have been found to protect membranes of red beet crown gall tissue more than their adjacent normal regions from thermal or gamma radiation stress, suggesting the possibility of an alteration on the surface charge accompanying tumor formation in plants. Further, tumor tissue has been observed to possess enhanced membrane ATPase activity, a higher tissue sulfhydryl content and increased protein levels, thus suggesting a model of source (normal tissue) and sink (tumor tissue) relationship.Acknowledgments. Thanks are due to Dr Sudhir Sopory, School of Life Sciences, Jawaharlal Nehru University, New Delhi for a critical discussion on this paper. KVAR thanks the Council of Scientific and Industrial Research, New Delhi, for financial assistance in the form of a Senior Research Fellowship.  相似文献   
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Nayar A 《Nature》2011,472(7341):24-26
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Summary An in situ method for measuring nitrate reductase (NR) in free-livingRhizobium cultures has been developed. Arginine, threonine, valine, glutamic acid, tyrosine and tryptophan were found to promote NR synthesis. In root nodules rhizobial nitrate reductase also converts nitrate into NH4 +, thus it provides an alternative to the nitrogenase route for the formation of NH4 +.Acknowledgments: M.H.S. is grateful to the authorities of CSIR, New Delhi and Miss Anjali Mathur to the authorities of SCST, Lucknow (U.P.) for financial assistance.  相似文献   
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We conducted a genome-wide association pooling study for cutaneous melanoma and performed validation in samples totaling 2,019 cases and 2,105 controls. Using pooling, we identified a new melanoma risk locus on chromosome 20 (rs910873 and rs1885120), with replication in two further samples (combined P < 1 x 10(-15)). The per allele odds ratio was 1.75 (1.53, 2.01), with evidence for stronger association in early-onset cases.  相似文献   
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Education: The PhD factory   总被引:3,自引:0,他引:3  
Cyranoski D  Gilbert N  Ledford H  Nayar A  Yahia M 《Nature》2011,472(7343):276-279
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Recombination, together with mutation, gives rise to genetic variation in populations. Here we leverage the recent mixture of people of African and European ancestry in the Americas to build a genetic map measuring the probability of crossing over at each position in the genome, based on about 2.1 million crossovers in 30,000 unrelated African Americans. At intervals of more than three megabases it is nearly identical to a map built in Europeans. At finer scales it differs significantly, and we identify about 2,500 recombination hotspots that are active in people of West African ancestry but nearly inactive in Europeans. The probability of a crossover at these hotspots is almost fully controlled by the alleles an individual carries at PRDM9 (P?value 相似文献   
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