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121.
Beyer KS Blasi F Bacchelli E Klauck SM Maestrini E Poustka A;International Molecular Genetic Study of Autism Consortium 《Human genetics》2002,111(4-5):305-309
Mutations in the coding region of the methyl-CpG-binding protein 2 ( MECP2) gene cause Rett syndrome and have also been reported in a number of X-linked mental retardation syndromes. Furthermore, such mutations have recently been described in a few autistic patients. In this study, a large sample of individuals with autism was screened in order to elucidate systematically whether specific mutations in MECP2 play a role in autism. The mutation analysis of the coding sequence of the gene was performed by denaturing high-pressure liquid chromatography and direct sequencing. Taken together, 14 sequence variants were identified in 152 autistic patients from 134 German families and 50 unrelated patients from the International Molecular Genetic Study of Autism Consortium affected relative-pair sample. Eleven of these variants were excluded for having an aetiological role as they were either silent mutations, did not cosegregate with autism in the pedigrees of the patients or represented known polymorphisms. The relevance of the three remaining mutations towards the aetiology of autism could not be ruled out, although they were not localised within functional domains of MeCP2 and may be rare polymorphisms. Taking into account the large size of our sample, we conclude that mutations in the coding region of MECP2 do not play a major role in autism susceptibility. Therefore, infantile autism and Rett syndrome probably represent two distinct entities at the molecular genetic level. 相似文献
122.
Nica AC Parts L Glass D Nisbet J Barrett A Sekowska M Travers M Potter S Grundberg E Small K Hedman AK Bataille V Tzenova Bell J Surdulescu G Dimas AS Ingle C Nestle FO di Meglio P Min JL Wilk A Hammond CJ Hassanali N Yang TP Montgomery SB O'Rahilly S Lindgren CM Zondervan KT Soranzo N Barroso I Durbin R Ahmadi K Deloukas P McCarthy MI Dermitzakis ET Spector TD;MuTHER Consortium 《PLoS genetics》2011,7(2):e1002003
While there have been studies exploring regulatory variation in one or more tissues, the complexity of tissue-specificity in multiple primary tissues is not yet well understood. We explore in depth the role of cis-regulatory variation in three human tissues: lymphoblastoid cell lines (LCL), skin, and fat. The samples (156 LCL, 160 skin, 166 fat) were derived simultaneously from a subset of well-phenotyped healthy female twins of the MuTHER resource. We discover an abundance of cis-eQTLs in each tissue similar to previous estimates (858 or 4.7% of genes). In addition, we apply factor analysis (FA) to remove effects of latent variables, thus more than doubling the number of our discoveries (1,822 eQTL genes). The unique study design (Matched Co-Twin Analysis--MCTA) permits immediate replication of eQTLs using co-twins (93%-98%) and validation of the considerable gain in eQTL discovery after FA correction. We highlight the challenges of comparing eQTLs between tissues. After verifying previous significance threshold-based estimates of tissue-specificity, we show their limitations given their dependency on statistical power. We propose that continuous estimates of the proportion of tissue-shared signals and direct comparison of the magnitude of effect on the fold change in expression are essential properties that jointly provide a biologically realistic view of tissue-specificity. Under this framework we demonstrate that 30% of eQTLs are shared among the three tissues studied, while another 29% appear exclusively tissue-specific. However, even among the shared eQTLs, a substantial proportion (10%-20%) have significant differences in the magnitude of fold change between genotypic classes across tissues. Our results underline the need to account for the complexity of eQTL tissue-specificity in an effort to assess consequences of such variants for complex traits. 相似文献
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125.
Bastian Schiffthaler Myrto Kostadima NGS Trainer Consortium Nicolas Delhomme Gabriella Rustici 《PLoS computational biology》2016,12(6)
The advancement of high-throughput sequencing (HTS) technologies and the rapid development of numerous analysis algorithms and pipelines in this field has resulted in an unprecedentedly high demand for training scientists in HTS data analysis. Embarking on developing new training materials is challenging for many reasons. Trainers often do not have prior experience in preparing or delivering such materials and struggle to keep them up to date. A repository of curated HTS training materials would support trainers in materials preparation, reduce the duplication of effort by increasing the usage of existing materials, and allow for the sharing of teaching experience among the HTS trainers’ community. To achieve this, we have developed a strategy for materials’ curation and dissemination. Standards for describing training materials have been proposed and applied to the curation of existing materials. A Git repository has been set up for sharing annotated materials that can now be reused, modified, or incorporated into new courses. This repository uses Git; hence, it is decentralized and self-managed by the community and can be forked/built-upon by all users. The repository is accessible at http://bioinformatics.upsc.se/htmr. 相似文献
126.
IntroductionFacial phenotype is influenced by genes and environment; however, little is known about their relative contributions to normal facial morphology. The aim of this study was to assess the relative genetic and environmental contributions to facial morphological variation using a three-dimensional (3D) population-based approach and the classical twin study design.ResultsHeritability of 13 uPC and 17 sPC reached statistical significance, with h2 ranging from 38.8% to 78.5% in the former and 30.5% to 84.8% in the latter group. Also, 1222 distances showed evidence of genetic control. Common environment contributed to one PC in both groups and 53 linear distances (4.3%). Unique environment contributed to 17 uPC and 20 sPC and 1245 distances.ConclusionsGenetic factors can explain more than 70% of the phenotypic facial variation in facial size, nose (width, prominence and height), lips prominence and inter-ocular distance. A few traits have shown potential dominant genetic influence: the prominence and height of the nose, the lower lip prominence in relation to the chin and upper lip philtrum length. Environmental contribution to facial variation seems to be the greatest for the mandibular ramus height and horizontal facial asymmetry. 相似文献
127.
Yannick Kronimus Alexandra Albus Monika Balzer-Geldsetzer Sarah Straub Elisa Semler Markus Otto Jens Klotsche Richard Dodel LANDSCAPE Consortium David Mengel 《PloS one》2016,11(11)
ResultsPDD patients had significantly decreased nAbs-tau serum levels compared to PDND patients (p = 0.007), whereas the serum titers of nAbs-αS and nAbs-Aβ were unchanged. For all three nAbs, no significant differences in avidity were found between PDD and PDND cohorts. However, within both patient groups, nAbs-tau showed lowest avidity to their antigen, followed by nAbs-αS, and nAbs-Aβ. Though, due to a high interassay coefficient of variability and the exclusion of many samples below the limit of detection, conclusions for nAbs-Aβ are only conditionally possible.ConclusionWe detected a significantly decreased nAbs-tau serum level in PDD patients, indicating a potential linkage between nAbs-tau serum titer and cognitive deficits in PD. Thus, further investigation in larger samples is justified to confirm our findings. 相似文献
128.
Xavier Grau-Bov Eric Lucas Dimitra Pipini Emily Rippon Arjn E. van t Hof Edi Constant Samuel Dadzie Alexander Egyir-Yawson John Essandoh Joseph Chabi Luc Djogbnou Nicholas J. Harding Alistair Miles Dominic Kwiatkowski Martin J. Donnelly David Weetman The Anopheles gambiae Genomes Consortium 《PLoS genetics》2021,17(1)
Vector population control using insecticides is a key element of current strategies to prevent malaria transmission in Africa. The introduction of effective insecticides, such as the organophosphate pirimiphos-methyl, is essential to overcome the recurrent emergence of resistance driven by the highly diverse Anopheles genomes. Here, we use a population genomic approach to investigate the basis of pirimiphos-methyl resistance in the major malaria vectors Anopheles gambiae and A. coluzzii. A combination of copy number variation and a single non-synonymous substitution in the acetylcholinesterase gene, Ace1, provides the key resistance diagnostic in an A. coluzzii population from Côte d’Ivoire that we used for sequence-based association mapping, with replication in other West African populations. The Ace1 substitution and duplications occur on a unique resistance haplotype that evolved in A. gambiae and introgressed into A. coluzzii, and is now common in West Africa primarily due to selection imposed by other organophosphate or carbamate insecticides. Our findings highlight the predictive value of this complex resistance haplotype for phenotypic resistance and clarify its evolutionary history, providing tools to for molecular surveillance of the current and future effectiveness of pirimiphos-methyl based interventions. 相似文献
129.
Gwenola Tosser-Klopp Philippe Bardou Olivier Bouchez Cédric Cabau Richard Crooijmans Yang Dong Cécile Donnadieu-Tonon André Eggen Henri C. M. Heuven Saadiah Jamli Abdullah Johari Jiken Christophe Klopp Cynthia T. Lawley John McEwan Patrice Martin Carole R. Moreno Philippe Mulsant Ibouniyamine Nabihoudine Eric Pailhoux Isabelle Palhière Rachel Rupp Julien Sarry Brian L. Sayre Aurélie Tircazes Jun Wang Wen Wang Wenguang Zhang International Goat Genome Consortium 《PloS one》2016,11(3)
130.
Schaid DJ McDonnell SK Zarfas KE Cunningham JM Hebbring S Thibodeau SN Eeles RA Easton DF Foulkes WD Simard J Giles GG Hopper JL Mahle L Moller P Badzioch M Bishop DT Evans C Edwards S Meitz J Bullock S Hope Q Guy M Hsieh CL Halpern J Balise RR Oakley-Girvan I Whittemore AS Xu J Dimitrov L Chang BL Adams TS Turner AR Meyers DA Friedrichsen DM Deutsch K Kolb S Janer M Hood L Ostrander EA Stanford JL Ewing CM Gielzak M Isaacs SD Walsh PC Wiley KE Isaacs WB Lange EM Ho LA Beebe-Dimmer JL Wood DP 《Human genetics》2006,120(4):471-485
While it is widely appreciated that prostate cancers vary substantially in their propensity to progress to a life-threatening
stage, the molecular events responsible for this progression have not been identified. Understanding these molecular mechanisms
could provide important prognostic information relevant to more effective clinical management of this heterogeneous cancer.
Hence, through genetic linkage analyses, we examined the hypothesis that the tendency to develop aggressive prostate cancer may have an important genetic component. Starting with 1,233 familial prostate cancer families with genome
scan data available from the International Consortium for Prostate Cancer Genetics, we selected those that had at least three
members with the phenotype of clinically aggressive prostate cancer, as defined by either high tumor grade and/or stage, resulting
in 166 pedigrees (13%). Genome-wide linkage data were then pooled to perform a combined linkage analysis for these families.
Linkage signals reaching a suggestive level of significance were found on chromosomes 6p22.3 (LOD = 3.0), 11q14.1–14.3 (LOD = 2.4),
and 20p11.21–q11.21 (LOD = 2.5). For chromosome 11, stronger evidence of linkage (LOD = 3.3) was observed among pedigrees
with an average at diagnosis of 65 years or younger. Other chromosomes that showed evidence for heterogeneity in linkage across
strata were chromosome 7, with the strongest linkage signal among pedigrees without male-to-male disease transmission (7q21.11,
LOD = 4.1), and chromosome 21, with the strongest linkage signal among pedigrees that had African American ancestry (21q22.13–22.3;
LOD = 3.2). Our findings suggest several regions that may contain genes which, when mutated, predispose men to develop a more
aggressive prostate cancer phenotype. This provides a basis for attempts to identify these genes, with potential clinical
utility for men with aggressive prostate cancer and their relatives.
The names of all authors and their affiliations are listed in the Acknowledgements. The fact that Dr Schaid’s name is given
here for purposes of correspondence should not be taken to imply that he played the sole leading part in writing this article.
An erratum to this article can be found at 相似文献