全文获取类型
收费全文 | 105篇 |
免费 | 1篇 |
国内免费 | 1篇 |
专业分类
系统科学 | 2篇 |
理论与方法论 | 2篇 |
现状及发展 | 19篇 |
研究方法 | 28篇 |
综合类 | 50篇 |
自然研究 | 6篇 |
出版年
2021年 | 1篇 |
2018年 | 2篇 |
2016年 | 3篇 |
2015年 | 1篇 |
2014年 | 6篇 |
2013年 | 5篇 |
2012年 | 10篇 |
2011年 | 17篇 |
2010年 | 1篇 |
2009年 | 1篇 |
2008年 | 7篇 |
2007年 | 6篇 |
2006年 | 12篇 |
2005年 | 9篇 |
2004年 | 3篇 |
2003年 | 3篇 |
2002年 | 6篇 |
1985年 | 1篇 |
1982年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1971年 | 1篇 |
1969年 | 2篇 |
1967年 | 2篇 |
1964年 | 1篇 |
1958年 | 1篇 |
1957年 | 1篇 |
排序方式: 共有107条查询结果,搜索用时 15 毫秒
101.
Morison IM Cramer Bordé EM Cheesman EJ Cheong PL Holyoake AJ Fichelson S Weeks RJ Lo A Davies SM Wilbanks SM Fagerlund RD Ludgate MW da Silva Tatley FM Coker MS Bockett NA Hughes G Pippig DA Smith MP Capron C Ledgerwood EC 《Nature genetics》2008,40(4):387-389
We report the first identified mutation in the gene encoding human cytochrome c (CYCS). Glycine 41, invariant throughout eukaryotes, is substituted by serine in a family with autosomal dominant thrombocytopenia caused by dysregulated platelet formation. The mutation yields a cytochrome c variant with enhanced apoptotic activity in vitro. Notably, the family has no other phenotypic indication of abnormal apoptosis, implying that cytochrome c activity is not a critical regulator of most physiological apoptosis. 相似文献
102.
Turner DJ Miretti M Rajan D Fiegler H Carter NP Blayney ML Beck S Hurles ME 《Nature genetics》2008,40(1):90-95
Meiotic recombination between highly similar duplicated sequences (nonallelic homologous recombination, NAHR) generates deletions, duplications, inversions and translocations, and it is responsible for genetic diseases known as 'genomic disorders', most of which are caused by altered copy number of dosage-sensitive genes. NAHR hot spots have been identified within some duplicated sequences. We have developed sperm-based assays to measure the de novo rate of reciprocal deletions and duplications at four NAHR hot spots. We used these assays to dissect the relative rates of NAHR between different pairs of duplicated sequences. We show that (i) these NAHR hot spots are specific to meiosis, (ii) deletions are generated at a higher rate than their reciprocal duplications in the male germline and (iii) some of these genomic disorders are likely to have been underascertained clinically, most notably that resulting from the duplication of 7q11, the reciprocal of the deletion causing Williams-Beuren syndrome. 相似文献
103.
Nbs1 is essential for DNA repair by homologous recombination in higher vertebrate cells 总被引:33,自引:0,他引:33
Tauchi H Kobayashi J Morishima K van Gent DC Shiraishi T Verkaik NS vanHeems D Ito E Nakamura A Sonoda E Takata M Takeda S Matsuura S Komatsu K 《Nature》2002,420(6911):93-98
Double-strand breaks occur during DNA replication and are also induced by ionizing radiation. There are at least two pathways which can repair such breaks: non-homologous end joining and homologous recombination (HR). Although these pathways are essentially independent of one another, it is possible that the proteins Mre11, Rad50 and Xrs2 are involved in both pathways in Saccharomyces cerevisiae. In vertebrate cells, little is known about the exact function of the Mre11-Rad50-Nbs1 complex in the repair of double-strand breaks because Mre11- and Rad50-null mutations are lethal. Here we show that Nbs1 is essential for HR-mediated repair in higher vertebrate cells. The disruption of Nbs1 reduces gene conversion and sister chromatid exchanges, similar to other HR-deficient mutants. In fact, a site-specific double-strand break repair assay showed a notable reduction of HR events following generation of such breaks in Nbs1-disrupted cells. The rare recombinants observed in the Nbs1-disrupted cells were frequently found to have aberrant structures, which possibly arise from unusual crossover events, suggesting that the Nbs1 complex might be required to process recombination intermediates. 相似文献
104.
105.
Suppression of lung adenocarcinoma progression by Nkx2-1 总被引:1,自引:0,他引:1
106.
Puente XS Pinyol M Quesada V Conde L Ordóñez GR Villamor N Escaramis G Jares P Beà S González-Díaz M Bassaganyas L Baumann T Juan M López-Guerra M Colomer D Tubío JM López C Navarro A Tornador C Aymerich M Rozman M Hernández JM Puente DA Freije JM Velasco G Gutiérrez-Fernández A Costa D Carrió A Guijarro S Enjuanes A Hernández L Yagüe J Nicolás P Romeo-Casabona CM Himmelbauer H Castillo E Dohm JC de Sanjosé S Piris MA de Alava E San Miguel J Royo R Gelpí JL Torrents D Orozco M Pisano DG 《Nature》2011,475(7354):101-105
Chronic lymphocytic leukaemia (CLL), the most frequent leukaemia in adults in Western countries, is a heterogeneous disease with variable clinical presentation and evolution. Two major molecular subtypes can be distinguished, characterized respectively by a high or low number of somatic hypermutations in the variable region of immunoglobulin genes. The molecular changes leading to the pathogenesis of the disease are still poorly understood. Here we performed whole-genome sequencing of four cases of CLL and identified 46 somatic mutations that potentially affect gene function. Further analysis of these mutations in 363 patients with CLL identified four genes that are recurrently mutated: notch 1 (NOTCH1), exportin 1 (XPO1), myeloid differentiation primary response gene 88 (MYD88) and kelch-like 6 (KLHL6). Mutations in MYD88 and KLHL6 are predominant in cases of CLL with mutated immunoglobulin genes, whereas NOTCH1 and XPO1 mutations are mainly detected in patients with unmutated immunoglobulins. The patterns of somatic mutation, supported by functional and clinical analyses, strongly indicate that the recurrent NOTCH1, MYD88 and XPO1 mutations are oncogenic changes that contribute to the clinical evolution of the disease. To our knowledge, this is the first comprehensive analysis of CLL combining whole-genome sequencing with clinical characteristics and clinical outcomes. It highlights the usefulness of this approach for the identification of clinically relevant mutations in cancer. 相似文献
107.
以蛋白核小球藻(Chlorella pyrenoidosa)为研究对象,考察了不同碳源及氮源对小球藻生物量和油脂产率的影响,确定了最佳碳源和氮源的添加量.结果表明,蛋白核小球藻最优碳源是葡萄糖,最优氮源是尿素;当葡萄糖浓度为30mg/L、尿素浓度为1.5mg/L时,小球藻生物量和油脂产率达到8783.9mg/L和126.3mg/L/d,比优化前分别提高了37.9%和125%.这为今后培养小球藻,提高其生物量和油脂产率奠定了一定的理论基础. 相似文献