全文获取类型
收费全文 | 83篇 |
免费 | 0篇 |
国内免费 | 2篇 |
专业分类
系统科学 | 1篇 |
理论与方法论 | 2篇 |
现状及发展 | 39篇 |
研究方法 | 12篇 |
综合类 | 25篇 |
自然研究 | 6篇 |
出版年
2020年 | 1篇 |
2018年 | 5篇 |
2017年 | 3篇 |
2016年 | 3篇 |
2015年 | 7篇 |
2014年 | 5篇 |
2013年 | 2篇 |
2012年 | 9篇 |
2011年 | 12篇 |
2010年 | 5篇 |
2009年 | 3篇 |
2008年 | 7篇 |
2007年 | 8篇 |
2006年 | 2篇 |
2005年 | 1篇 |
2004年 | 1篇 |
2003年 | 2篇 |
1997年 | 1篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1975年 | 1篇 |
1973年 | 1篇 |
排序方式: 共有85条查询结果,搜索用时 265 毫秒
81.
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
82.
Putoux A Thomas S Coene KL Davis EE Alanay Y Ogur G Uz E Buzas D Gomes C Patrier S Bennett CL Elkhartoufi N Frison MH Rigonnot L Joyé N Pruvost S Utine GE Boduroglu K Nitschke P Fertitta L Thauvin-Robinet C Munnich A Cormier-Daire V Hennekam R Colin E Akarsu NA Bole-Feysot C Cagnard N Schmitt A Goudin N Lyonnet S Encha-Razavi F Siffroi JP Winey M Katsanis N Gonzales M Vekemans M Beales PL Attié-Bitach T 《Nature genetics》2011,43(6):601-606
83.
Comino-Méndez I Gracia-Aznárez FJ Schiavi F Landa I Leandro-García LJ Letón R Honrado E Ramos-Medina R Caronia D Pita G Gómez-Graña A de Cubas AA Inglada-Pérez L Maliszewska A Taschin E Bobisse S Pica G Loli P Hernández-Lavado R Díaz JA Gómez-Morales M González-Neira A Roncador G Rodríguez-Antona C Benítez J Mannelli M Opocher G Robledo M Cascón A 《Nature genetics》2011,43(7):663-667
Hereditary pheochromocytoma (PCC) is often caused by germline mutations in one of nine susceptibility genes described to date, but there are familial cases without mutations in these known genes. We sequenced the exomes of three unrelated individuals with hereditary PCC (cases) and identified mutations in MAX, the MYC associated factor X gene. Absence of MAX protein in the tumors and loss of heterozygosity caused by uniparental disomy supported the involvement of MAX alterations in the disease. A follow-up study of a selected series of 59 cases with PCC identified five additional MAX mutations and suggested an association with malignant outcome and preferential paternal transmission of MAX mutations. The involvement of the MYC-MAX-MXD1 network in the development and progression of neural crest cell tumors is further supported by the lack of functional MAX in rat PCC (PC12) cells and by the amplification of MYCN in neuroblastoma and suggests that loss of MAX function is correlated with metastatic potential. 相似文献
84.
Thomas G Jacobs KB Yeager M Kraft P Wacholder S Orr N Yu K Chatterjee N Welch R Hutchinson A Crenshaw A Cancel-Tassin G Staats BJ Wang Z Gonzalez-Bosquet J Fang J Deng X Berndt SI Calle EE Feigelson HS Thun MJ Rodriguez C Albanes D Virtamo J Weinstein S Schumacher FR Giovannucci E Willett WC Cussenot O Valeri A Andriole GL Crawford ED Tucker M Gerhard DS Fraumeni JF Hoover R Hayes RB Hunter DJ Chanock SJ 《Nature genetics》2008,40(3):310-315
85.
The cellular basis of depressive disorders is poorly understood. Recent studies in monkeys indicate that neurons in the lateral habenula (LHb), a nucleus that mediates communication between forebrain and midbrain structures, can increase their activity when an animal fails to receive an expected positive reward or receives a stimulus that predicts aversive conditions (that is, disappointment or anticipation of a negative outcome). LHb neurons project to, and modulate, dopamine-rich regions, such as the ventral tegmental area (VTA), that control reward-seeking behaviour and participate in depressive disorders. Here we show that in two learned helplessness models of depression, excitatory synapses onto LHb neurons projecting to the VTA are potentiated. Synaptic potentiation correlates with an animal's helplessness behaviour and is due to an enhanced presynaptic release probability. Depleting transmitter release by repeated electrical stimulation of LHb afferents, using a protocol that can be effective for patients who are depressed, markedly suppresses synaptic drive onto VTA-projecting LHb neurons in brain slices and can significantly reduce learned helplessness behaviour in rats. Our results indicate that increased presynaptic action onto LHb neurons contributes to the rodent learned helplessness model of depression. 相似文献