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排序方式: 共有119条查询结果,搜索用时 21 毫秒
101.
Jennifer R. Malinowski Joshua C. Denny Suzette J. Bielinski Melissa A. Basford Yuki Bradford Peggy L. Peissig David Carrell David R. Crosslin Jyotishman Pathak Luke Rasmussen Jennifer Pacheco Abel Kho Katherine M. Newton Rongling Li Iftikhar J. Kullo Christopher G. Chute Rex L. Chisholm Gail P. Jarvik Eric B. Larson Catherine A. McCarty Daniel R. Masys Dan M. Roden Mariza de Andrade Marylyn D. Ritchie Dana C. Crawford 《PloS one》2014,9(12)
Thyroid stimulating hormone (TSH) hormone levels are normally tightly regulated within an individual; thus, relatively small variations may indicate thyroid disease. Genome-wide association studies (GWAS) have identified variants in PDE8B and FOXE1 that are associated with TSH levels. However, prior studies lacked racial/ethnic diversity, limiting the generalization of these findings to individuals of non-European ethnicities. The Electronic Medical Records and Genomics (eMERGE) Network is a collaboration across institutions with biobanks linked to electronic medical records (EMRs). The eMERGE Network uses EMR-derived phenotypes to perform GWAS in diverse populations for a variety of phenotypes. In this report, we identified serum TSH levels from 4,501 European American and 351 African American euthyroid individuals in the eMERGE Network with existing GWAS data. Tests of association were performed using linear regression and adjusted for age, sex, body mass index (BMI), and principal components, assuming an additive genetic model. Our results replicate the known association of PDE8B with serum TSH levels in European Americans (rs2046045 p = 1.85×10−17, β = 0.09). FOXE1 variants, associated with hypothyroidism, were not genome-wide significant (rs10759944: p = 1.08×10−6, β = −0.05). No SNPs reached genome-wide significance in African Americans. However, multiple known associations with TSH levels in European ancestry were nominally significant in African Americans, including PDE8B (rs2046045 p = 0.03, β = −0.09), VEGFA (rs11755845 p = 0.01, β = −0.13), and NFIA (rs334699 p = 1.50×10−3, β = −0.17). We found little evidence that SNPs previously associated with other thyroid-related disorders were associated with serum TSH levels in this study. These results support the previously reported association between PDE8B and serum TSH levels in European Americans and emphasize the need for additional genetic studies in more diverse populations. 相似文献
102.
The miR‐379/miR‐410 cluster at the imprinted Dlk1‐Dio3 domain controls neonatal metabolic adaptation
Marie‐Line Bortolin‐Cavaillé Magali Hoareau‐Osman Jean‐Philippe Pradère Philippe Valet Pascal GP Martin Jérôme Cavaillé 《The EMBO journal》2014,33(19):2216-2230
In mammals, birth entails complex metabolic adjustments essential for neonatal survival. Using a mouse knockout model, we identify crucial biological roles for the miR‐379/miR‐410 cluster within the imprinted Dlk1‐Dio3 region during this metabolic transition. The miR‐379/miR‐410 locus, also named C14MC in humans, is the largest known placental mammal‐specific miRNA cluster, whose 39 miRNA genes are expressed only from the maternal allele. We found that heterozygote pups with a maternal—but not paternal—deletion of the miRNA cluster display partially penetrant neonatal lethality with defects in the maintenance of energy homeostasis. This maladaptive metabolic response is caused, at least in part, by profound changes in the activation of the neonatal hepatic gene expression program, pointing to as yet unidentified regulatory pathways that govern this crucial metabolic transition in the newborn's liver. Not only does our study highlight the physiological importance of miRNA genes that recently evolved in placental mammal lineages but it also unveils additional layers of RNA‐mediated gene regulation at the Dlk1‐Dio3 domain that impose parent‐of‐origin effects on metabolic control at birth and have likely contributed to mammal evolution. 相似文献
103.
Khader Shameer Joshua C. Denny Keyue Ding Hayan Jouni David R. Crosslin Mariza de Andrade Christopher G. Chute Peggy Peissig Jennifer A. Pacheco Rongling Li Lisa Bastarache Abel N. Kho Marylyn D. Ritchie Daniel R. Masys Rex L. Chisholm Eric B. Larson Catherine A. McCarty Dan M. Roden Gail P. Jarvik Iftikhar J. Kullo 《Human genetics》2014,133(1):95-109
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105.
Ellen M. Wijsman Joseph H. Rothstein Robert P. Igo Jr. John D. Brunzell Arno G. Motulsky Gail P. Jarvik 《Human genetics》2010,127(6):705-719
Familial combined hyperlipidemia (FCHL) is a complex trait leading to cardiovascular disease (CVD) risk. Elevated levels and
size of apolipoprotein B (apoB) and low-density lipoprotein (LDL) are associated with FCHL, which is genetically heterogeneous
and is likely caused by rare variants. We carried out a linkage-based genome scan of four large FCHL pedigrees for apoB level
that is independent of LDL: apoB level that is adjusted for LDL level and size. Follow-up included SNP genotyping in the region
with the strongest evidence of linkage. Several regions with the evidence of linkage in individual pedigrees support the rare
variant model. Evidence of linkage was strongest on chromosome 4q, with multipoint analysis in one pedigree giving LOD = 3.1
with a parametric model, and a log Bayes Factor = 1.5 from a Bayesian oligogenic approach. Of the 293 SNPs spanning the implicated
region on 4q, rs6829588 completely explained the evidence of linkage. This SNP accounted for 39% of the apoB phenotypic variance,
with heterozygotes for this SNP having a trait value that was ~30% higher than that of the high-frequency homozygote, thus
identifying and considerably refining a strong candidate region. These results illustrate the advantage of using large pedigrees
in the search for rare variants: reduced genetic heterogeneity within single pedigrees coupled with the large number of individuals
segregating otherwise-rare single variants leads to high power to implicate such variants. 相似文献
106.
Targeted isolation of simple sequence repeat markers through the use of bacterial artificial chromosomes 总被引:11,自引:0,他引:11
P. B. Cregan J. Mudge E. W. Fickus L. F. Marek D. Danesh R. Denny R. C. Shoemaker B. F. Matthews T. Jarvik N. D. Young 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1999,98(6-7):919-928
Simple sequence repeats (SSRs) are versatile DNA markers that are readily assayed and highly informative. Unfortunately,
non-targeted approaches to SSR development often leave large genomic regions without SSR markers. In some cases these same
genomic regions are already populated by other types of DNA markers, especially restriction fragment length polymorphisms
(RFLPs), random amplified polymorphic DNAs (RAPDs), and amplified fragment length polymorphisms (AFLPs). To identify SSR markers
in such regions, bacterial artificial chromosome (BAC) clones can be used as intermediaries. First, one or more BAC clones
in a region of interest are identified through the use of an existing DNA marker. BAC clones uncovered in this initial step
are then used to create a small insert DNA library that can be screened for the presence of SSR-containing clones. Because
BAC inserts are often 100-kb pairs or more in size, most contain one or more SSRs. This strategy was applied to two regions
of the soybean genome near genes that condition resistance to the soybean cyst nematode on molecular linkage groups G and
A2. This targeted approach to identifying new DNA markers can readily be extended to other types of DNA markers, including
single nucleotide polymorphisms.
Received: 13 August 1998 / Accepted: 13 October 1998 相似文献
107.
108.
In an initial study, differences in learning and immediate recall were observed for groups of young and aged subjects on several measures. Retest date showed some differential loss for aged subjects after 1 week. Conclusions regarding long-term retention per se were not possible due to the nature of the design. In a second study, additional aged and young groups of subjects were run under delayed recall conditions. The data from these two groups were combined with data from the first study, with care taken to match subjects on a number of variables (health, education, intelligence). The results showed age-related differences for measures of learning and immediate recall but not for delayed 1 week retention. 相似文献
109.
110.