全文获取类型
收费全文 | 129篇 |
免费 | 0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 | 37篇 |
研究方法 | 26篇 |
综合类 | 62篇 |
自然研究 | 1篇 |
出版年
2021年 | 1篇 |
2020年 | 1篇 |
2019年 | 1篇 |
2018年 | 1篇 |
2017年 | 1篇 |
2016年 | 1篇 |
2015年 | 4篇 |
2014年 | 2篇 |
2013年 | 3篇 |
2012年 | 12篇 |
2011年 | 14篇 |
2010年 | 4篇 |
2008年 | 10篇 |
2007年 | 11篇 |
2006年 | 5篇 |
2005年 | 9篇 |
2004年 | 6篇 |
2003年 | 8篇 |
2002年 | 9篇 |
2001年 | 1篇 |
2000年 | 1篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1985年 | 1篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1978年 | 1篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1969年 | 2篇 |
1968年 | 1篇 |
1964年 | 1篇 |
1956年 | 1篇 |
1955年 | 3篇 |
排序方式: 共有130条查询结果,搜索用时 0 毫秒
71.
Yu TW Mochida GH Tischfield DJ Sgaier SK Flores-Sarnat L Sergi CM Topçu M McDonald MT Barry BJ Felie JM Sunu C Dobyns WB Folkerth RD Barkovich AJ Walsh CA 《Nature genetics》2010,42(11):1015-1020
Genes associated with human microcephaly, a condition characterized by a small brain, include critical regulators of proliferation, cell fate and DNA repair. We describe a syndrome of congenital microcephaly and diverse defects in cerebral cortical architecture. Genome-wide linkage analysis in two families identified a 7.5-Mb locus on chromosome 19q13.12 containing 148 genes. Targeted high throughput sequence analysis of linked genes in each family yielded > 4,000 DNA variants and implicated a single gene, WDR62, as harboring potentially deleterious changes. We subsequently identified additional WDR62 mutations in four other families. Magnetic resonance imaging and postmortem brain analysis supports important roles for WDR62 in the proliferation and migration of neuronal precursors. WDR62 is a WD40 repeat-containing protein expressed in neuronal precursors as well as in postmitotic neurons in the developing brain and localizes to the spindle poles of dividing cells. The diverse phenotypes of WDR62 suggest it has central roles in many aspects of cerebral cortical development. 相似文献
72.
McLellan JS Pancera M Carrico C Gorman J Julien JP Khayat R Louder R Pejchal R Sastry M Dai K O'Dell S Patel N Shahzad-ul-Hussan S Yang Y Zhang B Zhou T Zhu J Boyington JC Chuang GY Diwanji D Georgiev I Kwon YD Lee D Louder MK Moquin S Schmidt SD Yang ZY Bonsignori M Crump JA Kapiga SH Sam NE Haynes BF Burton DR Koff WC Walker LM Phogat S Wyatt R Orwenyo J Wang LX Arthos J Bewley CA Mascola JR Nabel GJ Schief WR Ward AB Wilson IA Kwong PD 《Nature》2011,480(7377):336-343
Variable regions 1 and 2 (V1/V2) of human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein are critical for viral evasion of antibody neutralization, and are themselves protected by extraordinary sequence diversity and N-linked glycosylation. Human antibodies such as PG9 nonetheless engage V1/V2 and neutralize 80% of HIV-1 isolates. Here we report the structure of V1/V2 in complex with PG9. V1/V2 forms a four-stranded β-sheet domain, in which sequence diversity and glycosylation are largely segregated to strand-connecting loops. PG9 recognition involves electrostatic, sequence-independent and glycan interactions: the latter account for over half the interactive surface but are of sufficiently weak affinity to avoid autoreactivity. The structures of V1/V2-directed antibodies CH04 and PGT145 indicate that they share a common mode of glycan penetration by extended anionic loops. In addition to structurally defining V1/V2, the results thus identify a paradigm of antibody recognition for highly glycosylated antigens, which-with PG9-involves a site of vulnerability comprising just two glycans and a strand. 相似文献
73.
74.
Mühlebach MD Mateo M Sinn PL Prüfer S Uhlig KM Leonard VH Navaratnarajah CK Frenzke M Wong XX Sawatsky B Ramachandran S McCray PB Cichutek K von Messling V Lopez M Cattaneo R 《Nature》2011,480(7378):530-533
Measles virus is an aerosol-transmitted virus that affects more than 10 million children each year and accounts for approximately 120,000 deaths. Although it was long believed to replicate in the respiratory epithelium before disseminating, it was recently shown to infect initially macrophages and dendritic cells of the airways using signalling lymphocytic activation molecule family member 1 (SLAMF1; also called CD150) as a receptor. These cells then cross the respiratory epithelium and transport the infection to lymphatic organs where measles virus replicates vigorously. How and where the virus crosses back into the airways has remained unknown. On the basis of functional analyses of surface proteins preferentially expressed on virus-permissive human epithelial cell lines, here we identify nectin-4 (ref. 8; also called poliovirus-receptor-like-4 (PVRL4)) as a candidate host exit receptor. This adherens junction protein of the immunoglobulin superfamily interacts with the viral attachment protein with high affinity through its membrane-distal domain. Nectin-4 sustains measles virus entry and non-cytopathic lateral spread in well-differentiated primary human airway epithelial sheets infected basolaterally. It is downregulated in infected epithelial cells, including those of macaque tracheae. Although other viruses use receptors to enter hosts or transit through their epithelial barriers, we suggest that measles virus targets nectin-4 to emerge in the airways. Nectin-4 is a cellular marker of several types of cancer, which has implications for ongoing measles-virus-based clinical trials of oncolysis. 相似文献
75.
76.
77.
78.
79.
Marie Lacan Christine Keyser Eric Crubézy Bertrand Ludes 《Cellular and molecular life sciences : CMLS》2013,70(14):2473-2487
Understanding the peopling history of Europe is crucial to comprehend the origins of modern populations. Of course, the analysis of current genetic data offers several explanations about human migration patterns which occurred on this continent, but it fails to explain precisely the impact of each demographic event. In this context, direct access to the DNA of ancient specimens allows the overcoming of recent demographic phenomena, which probably highly modified the constitution of the current European gene pool. In recent years, several DNA studies have been successfully conducted from ancient human remains thanks to the improvement of molecular techniques. They have brought new fundamental information on the peopling of Europe and allowed us to refine our understanding of European prehistory. In this review, we will detail all the ancient DNA studies performed to date on ancient European DNA from the Middle Paleolithic to the beginning of the protohistoric period. 相似文献
80.