全文获取类型
收费全文 | 670篇 |
免费 | 2篇 |
国内免费 | 6篇 |
专业分类
系统科学 | 9篇 |
教育与普及 | 2篇 |
理论与方法论 | 20篇 |
现状及发展 | 75篇 |
研究方法 | 102篇 |
综合类 | 383篇 |
自然研究 | 87篇 |
出版年
2022年 | 1篇 |
2021年 | 2篇 |
2020年 | 1篇 |
2019年 | 2篇 |
2018年 | 2篇 |
2017年 | 4篇 |
2016年 | 9篇 |
2015年 | 4篇 |
2014年 | 3篇 |
2013年 | 10篇 |
2012年 | 43篇 |
2011年 | 146篇 |
2010年 | 28篇 |
2009年 | 4篇 |
2008年 | 51篇 |
2007年 | 49篇 |
2006年 | 46篇 |
2005年 | 56篇 |
2004年 | 60篇 |
2003年 | 53篇 |
2002年 | 45篇 |
2001年 | 1篇 |
2000年 | 5篇 |
1999年 | 6篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 4篇 |
1988年 | 4篇 |
1986年 | 2篇 |
1985年 | 6篇 |
1984年 | 6篇 |
1982年 | 2篇 |
1980年 | 3篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1972年 | 1篇 |
1966年 | 1篇 |
1965年 | 2篇 |
1958年 | 1篇 |
1957年 | 1篇 |
1955年 | 2篇 |
排序方式: 共有678条查询结果,搜索用时 15 毫秒
591.
592.
593.
Rivière JB van Bon BW Hoischen A Kholmanskikh SS O'Roak BJ Gilissen C Gijsen S Sullivan CT Christian SL Abdul-Rahman OA Atkin JF Chassaing N Drouin-Garraud V Fry AE Fryns JP Gripp KW Kempers M Kleefstra T Mancini GM Nowaczyk MJ van Ravenswaaij-Arts CM Roscioli T Marble M Rosenfeld JA Siu VM de Vries BB Shendure J Verloes A Veltman JA Brunner HG Ross ME Pilz DT Dobyns WB 《Nature genetics》2012,44(4):440-4, S1-2
Brain malformations are individually rare but collectively common causes of developmental disabilities. Many forms of malformation occur sporadically and are associated with reduced reproductive fitness, pointing to a causative role for de novo mutations. Here, we report a study of Baraitser-Winter syndrome, a well-defined disorder characterized by distinct craniofacial features, ocular colobomata and neuronal migration defect. Using whole-exome sequencing of three proband-parent trios, we identified de novo missense changes in the cytoplasmic actin-encoding genes ACTB and ACTG1 in one and two probands, respectively. Sequencing of both genes in 15 additional affected individuals identified disease-causing mutations in all probands, including two recurrent de novo alterations (ACTB, encoding p.Arg196His, and ACTG1, encoding p.Ser155Phe). Our results confirm that trio-based exome sequencing is a powerful approach to discover genes causing sporadic developmental disorders, emphasize the overlapping roles of cytoplasmic actin proteins in development and suggest that Baraitser-Winter syndrome is the predominant phenotype associated with mutation of these two genes. 相似文献
594.
William O.C. Symondson Jeremy D. Holloway Benoit Goossens Carsten T. Müller 《Journal of Natural History》2015,49(9-10):553-560
Many Lepidoptera larvae use pieces of vegetation bound with silk to construct or disguise their cocoons. Here we report the first known case of a caterpillar building its cocoon entirely out of fragments of resin, broken away from sheets of dried resin on the trunk of a tree and held together with silk. The behaviour of the larva (possibly Negritothripa sp. in the Nolidae), from the Kinabatangan Wildlife Sanctuary in Sabah, Borneo, is described. The cocoon was constructed on the trunk of Vatica rassak (Dipterocarpaceae). Analysis of resin from the cocoon, using gas chromatography-mass spectrometry, revealed a complex mixture of 260 components, dominated by sesquiterpenes and triterpenes. Many of these compounds have defensive properties, protecting the tree from herbivores and fungi. The larva appears to have evolved an elaborate and possibly unique behaviour, allowing it to harness the defensive properties of the resin to protect its pupa from predators and/or entomopathogenic fungi. 相似文献
595.
Yang J Manolio TA Pasquale LR Boerwinkle E Caporaso N Cunningham JM de Andrade M Feenstra B Feingold E Hayes MG Hill WG Landi MT Alonso A Lettre G Lin P Ling H Lowe W Mathias RA Melbye M Pugh E Cornelis MC Weir BS Goddard ME Visscher PM 《Nature genetics》2011,43(6):519-525
We estimate and partition genetic variation for height, body mass index (BMI), von Willebrand factor and QT interval (QTi) using 586,898 SNPs genotyped on 11,586 unrelated individuals. We estimate that ~45%, ~17%, ~25% and ~21% of the variance in height, BMI, von Willebrand factor and QTi, respectively, can be explained by all autosomal SNPs and a further ~0.5-1% can be explained by X chromosome SNPs. We show that the variance explained by each chromosome is proportional to its length, and that SNPs in or near genes explain more variation than SNPs between genes. We propose a new approach to estimate variation due to cryptic relatedness and population stratification. Our results provide further evidence that a substantial proportion of heritability is captured by common SNPs, that height, BMI and QTi are highly polygenic traits, and that the additive variation explained by a part of the genome is approximately proportional to the total length of DNA contained within genes therein. 相似文献
596.
Barak T Kwan KY Louvi A Demirbilek V Saygı S Tüysüz B Choi M Boyacı H Doerschner K Zhu Y Kaymakçalan H Yılmaz S Bakırcıoğlu M Cağlayan AO Oztürk AK Yasuno K Brunken WJ Atalar E Yalçınkaya C Dinçer A Bronen RA Mane S Ozçelik T Lifton RP Sestan N Bilgüvar K Günel M 《Nature genetics》2011,43(6):590-594
The biological basis for regional and inter-species differences in cerebral cortical morphology is poorly understood. We focused on consanguineous Turkish families with a single affected member with complex bilateral occipital cortical gyration abnormalities. By using whole-exome sequencing, we initially identified a homozygous 2-bp deletion in LAMC3, the laminin γ3 gene, leading to an immediate premature termination codon. In two other affected individuals with nearly identical phenotypes, we identified a homozygous nonsense mutation and a compound heterozygous mutation. In human but not mouse fetal brain, LAMC3 is enriched in postmitotic cortical plate neurons, localizing primarily to the somatodendritic compartment. LAMC3 expression peaks between late gestation and late infancy, paralleling the expression of molecules that are important in dendritogenesis and synapse formation. The discovery of the molecular basis of this unusual occipital malformation furthers our understanding of the complex biology underlying the formation of cortical gyrations. 相似文献
597.
INTERMEDIUM-C, a modifier of lateral spikelet fertility in barley, is an ortholog of the maize domestication gene TEOSINTE BRANCHED 1 总被引:1,自引:0,他引:1
Ramsay L Comadran J Druka A Marshall DF Thomas WT Macaulay M MacKenzie K Simpson C Fuller J Bonar N Hayes PM Lundqvist U Franckowiak JD Close TJ Muehlbauer GJ Waugh R 《Nature genetics》2011,43(2):169-172
The domestication of cereals has involved common changes in morphological features, such as seed size, seed retention and modification of vegetative and inflorescence architecture that ultimately contributed to an increase in harvested yield. In barley, this process has resulted in two different cultivated types, two-rowed and six-rowed forms, both derived from the wild two-rowed ancestor, with archaeo-botanical evidence indicating the origin of six-rowed barley early in the domestication of the species, some 8,600-8,000 years ago. Variation at SIX-ROWED SPIKE 1 (VRS1) is sufficient to control this phenotype. However, phenotypes imposed by VRS1 alleles are modified by alleles at the INTERMEDIUM-C (INT-C) locus. Here we show that INT-C is an ortholog of the maize domestication gene TEOSINTE BRANCHED 1 (TB1) and identify 17 coding mutations in barley TB1 correlated with lateral spikelet fertility phenotypes. 相似文献
598.
Hennies HC Kornak U Zhang H Egerer J Zhang X Seifert W Kühnisch J Budde B Nätebus M Brancati F Wilcox WR Müller D Kaplan PB Rajab A Zampino G Fodale V Dallapiccola B Newman W Metcalfe K Clayton-Smith J Tassabehji M Steinmann B Barr FA Nürnberg P Wieacker P Mundlos S 《Nature genetics》2008,40(12):1410-1412
Gerodermia osteodysplastica is an autosomal recessive disorder characterized by wrinkly skin and osteoporosis. Here we demonstrate that gerodermia osteodysplastica is caused by loss-of-function mutations in SCYL1BP1, which is highly expressed in skin and osteoblasts. The protein localizes to the Golgi apparatus and interacts with Rab6, identifying SCYL1BP1 as a golgin. These results associate abnormalities of the secretory pathway with age-related changes in connective tissues. 相似文献
599.
Katona RL Sinkó I Holló G Szucs KS Praznovszky T Kereso J Csonka E Fodor K Cserpán I Szakál B Blazsó P Udvardy A Hadlaczky G 《Cellular and molecular life sciences : CMLS》2008,65(23):3830-3838
Mammalian artificial chromosomes (MACs) are safe, stable, non-integrating genetic vectors with almost unlimited therapeutic
transgene-carrying capacity. The combination of MAC and stem cell technologies offers a new strategy for stem cell-based therapy,
the efficacy of which was confirmed and validated by using a mouse model of a devastating monogenic disease, galactocerebrosidase
deficiency (Krabbe’s disease). Therapeutic MACs were generated by sequence-specific loading of galactocerebrosidase transgenes
into a platform MAC, and stable, pluripotent mouse embryonic stem cell lines were established with these chromosomes. The
transgenic stem cells were thoroughly characterized and used to produce chimeric mice on the mutant genetic background. The
lifespan of these chimeras was increased twofold, verifying the feasibility of the development of MAC-stem cell systems for
the delivery of therapeutic genes in stem cells to treat genetic diseases and cancers, and to produce cell types for cell
replacement therapies.
Received 29 July 2008; received after revision 22 September 2008; accepted 24 September 2008 相似文献
600.
Hunt KA Zhernakova A Turner G Heap GA Franke L Bruinenberg M Romanos J Dinesen LC Ryan AW Panesar D Gwilliam R Takeuchi F McLaren WM Holmes GK Howdle PD Walters JR Sanders DS Playford RJ Trynka G Mulder CJ Mearin ML Verbeek WH Trimble V Stevens FM O'Morain C Kennedy NP Kelleher D Pennington DJ Strachan DP McArdle WL Mein CA Wapenaar MC Deloukas P McGinnis R McManus R Wijmenga C van Heel DA 《Nature genetics》2008,40(4):395-402
Our genome-wide association study of celiac disease previously identified risk variants in the IL2-IL21 region. To identify additional risk variants, we genotyped 1,020 of the most strongly associated non-HLA markers in an additional 1,643 cases and 3,406 controls. Through joint analysis including the genome-wide association study data (767 cases, 1,422 controls), we identified seven previously unknown risk regions (P < 5 x 10(-7)). Six regions harbor genes controlling immune responses, including CCR3, IL12A, IL18RAP, RGS1, SH2B3 (nsSNP rs3184504) and TAGAP. Whole-blood IL18RAP mRNA expression correlated with IL18RAP genotype. Type 1 diabetes and celiac disease share HLA-DQ, IL2-IL21, CCR3 and SH2B3 risk regions. Thus, this extensive genome-wide association follow-up study has identified additional celiac disease risk variants in relevant biological pathways. 相似文献