全文获取类型
收费全文 | 238篇 |
免费 | 0篇 |
专业分类
系统科学 | 2篇 |
理论与方法论 | 1篇 |
现状及发展 | 42篇 |
研究方法 | 26篇 |
综合类 | 155篇 |
自然研究 | 12篇 |
出版年
2018年 | 1篇 |
2014年 | 1篇 |
2013年 | 1篇 |
2012年 | 13篇 |
2011年 | 26篇 |
2010年 | 4篇 |
2008年 | 10篇 |
2007年 | 9篇 |
2006年 | 10篇 |
2005年 | 15篇 |
2004年 | 10篇 |
2003年 | 11篇 |
2002年 | 19篇 |
2001年 | 7篇 |
2000年 | 8篇 |
1999年 | 2篇 |
1998年 | 2篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1992年 | 3篇 |
1991年 | 1篇 |
1989年 | 3篇 |
1988年 | 6篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 6篇 |
1984年 | 6篇 |
1983年 | 3篇 |
1981年 | 2篇 |
1980年 | 5篇 |
1979年 | 1篇 |
1978年 | 5篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1974年 | 5篇 |
1973年 | 3篇 |
1972年 | 3篇 |
1971年 | 5篇 |
1970年 | 7篇 |
1969年 | 2篇 |
1968年 | 2篇 |
1967年 | 4篇 |
1966年 | 4篇 |
1965年 | 2篇 |
1958年 | 3篇 |
排序方式: 共有238条查询结果,搜索用时 37 毫秒
181.
Diurnal shedding by retinal rods was studied in wild cutthroat trout,Oncorhyncus clarki, hatchery rainbow trout,Oncorhyncus mykiss, and the plains killifish,Fundulus zebrinus, by counting the shed tips of rod outer segments ingested as phagosomes by pigment epithelial cells. After sunrise, phagosomes increased in all species, but fewer occurred in trout, and these were elevated from 3 to 9 hours after sunrise. Shedding occurred earlier in the light period and was more robust in killifish, with phagosomes elevated from 1.5 to 6 hours after sunset. The data suggest that both production of phagosomes by shedding and their subsequent disposal are slower at the lower temperatures experienced by trout. Otherwise, rod shedding produced under natural lighting is not appreciably different than that provoked by sudden onset of artificial light. 相似文献
182.
183.
Evidence for apostatic selection by wild passerines 总被引:2,自引:0,他引:2
184.
Barbieri CE Baca SC Lawrence MS Demichelis F Blattner M Theurillat JP White TA Stojanov P Van Allen E Stransky N Nickerson E Chae SS Boysen G Auclair D Onofrio RC Park K Kitabayashi N MacDonald TY Sheikh K Vuong T Guiducci C Cibulskis K Sivachenko A Carter SL Saksena G Voet D Hussain WM Ramos AH Winckler W Redman MC Ardlie K Tewari AK Mosquera JM Rupp N Wild PJ Moch H Morrissey C Nelson PS Kantoff PW Gabriel SB Golub TR Meyerson M Lander ES Getz G Rubin MA Garraway LA 《Nature genetics》2012,44(6):685-689
185.
186.
Genetic Analysis of Psoriasis Consortium & the Wellcome Trust Case Control Consortium Strange A Capon F Spencer CC Knight J Weale ME Allen MH Barton A Band G Bellenguez C Bergboer JG Blackwell JM Bramon E Bumpstead SJ Casas JP Cork MJ Corvin A Deloukas P Dilthey A Duncanson A Edkins S Estivill X Fitzgerald O Freeman C Giardina E Gray E Hofer A Hüffmeier U Hunt SE Irvine AD Jankowski J Kirby B Langford C Lascorz J Leman J Leslie S Mallbris L Markus HS Mathew CG McLean WH McManus R 《Nature genetics》2010,42(11):985-990
To identify new susceptibility loci for psoriasis, we undertook a genome-wide association study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified associations at eight previously unreported genomic loci. Seven loci harbored genes with recognized immune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These associations were replicated in 9,079 European samples (six loci with a combined P < 5 × 10?? and two loci with a combined P < 5 × 10??). We also report compelling evidence for an interaction between the HLA-C and ERAP1 loci (combined P = 6.95 × 10??). ERAP1 plays an important role in MHC class I peptide processing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk allele. Our findings implicate pathways that integrate epidermal barrier dysfunction with innate and adaptive immune dysregulation in psoriasis pathogenesis. 相似文献
187.
Haiman CA Chen GK Blot WJ Strom SS Berndt SI Kittles RA Rybicki BA Isaacs WB Ingles SA Stanford JL Diver WR Witte JS Hsing AW Nemesure B Rebbeck TR Cooney KA Xu J Kibel AS Hu JJ John EM Gueye SM Watya S Signorello LB Hayes RB Wang Z Yeboah E Tettey Y Cai Q Kolb S Ostrander EA Zeigler-Johnson C Yamamura Y Neslund-Dudas C Haslag-Minoff J Wu W Thomas V Allen GO Murphy A Chang BL Zheng SL Leske MC Wu SY Ray AM Hennis AJ Thun MJ Carpten J Casey G Carter EN Duarte ER Xia LY Sheng X Wan P Pooler LC 《Nature genetics》2011,43(6):570-573
In search of common risk alleles for prostate cancer that could contribute to high rates of the disease in men of African ancestry, we conducted a genome-wide association study, with 1,047,986 SNP markers examined in 3,425 African-Americans with prostate cancer (cases) and 3,290 African-American male controls. We followed up the most significant 17 new associations from stage 1 in 1,844 cases and 3,269 controls of African ancestry. We identified a new risk variant on chromosome 17q21 (rs7210100, odds ratio per allele = 1.51, P = 3.4 × 10(-13)). The frequency of the risk allele is ~5% in men of African descent, whereas it is rare in other populations (<1%). Further studies are needed to investigate the biological contribution of this allele to prostate cancer risk. These findings emphasize the importance of conducting genome-wide association studies in diverse populations. 相似文献
188.
Cooper JD Smyth DJ Smiles AM Plagnol V Walker NM Allen JE Downes K Barrett JC Healy BC Mychaleckyj JC Warram JH Todd JA 《Nature genetics》2008,40(12):1399-1401
We carried out a meta-analysis of data from three genome-wide association (GWA) studies of type 1 diabetes (T1D), testing 305,090 SNPs in 3,561 T1D cases and 4,646 controls of European ancestry. We obtained further support for 4q27 (IL2-IL21, P = 1.9 x 10(-8)) and, after genotyping an additional 6,225 cases, 6,946 controls and 2,828 families, convincing evidence for four previously unknown and distinct risk loci in chromosome regions 6q15 (BACH2, P = 4.7 x 10(-12)), 10p15 (PRKCQ, P = 3.7 x 10(-9)), 15q24 (CTSH, P = 3.2 x 10(-15)) and 22q13 (C1QTNF6, P = 2.0 x 10(-8)). 相似文献
189.
The catalase-peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis. 总被引:82,自引:0,他引:82
Tuberculosis is responsible for one in four of all avoidable adult deaths in developing countries. Increased frequency and accelerated fatality of the disease among individuals infected with human immunodeficiency virus has raised worldwide concern that control programmes may be inadequate, and the emergence of multidrug-resistant strains of Mycobacterium tuberculosis has resulted in several recent fatal outbreaks in the United States. Isonicotinic acid hydrazide (isoniazid, INH) forms the core of antituberculosis regimens; however, clinical isolates that are resistant to INH show reduced catalase activity and a relative lack of virulence in guinea-pigs. Here we use mycobacterial genetics to study the molecular basis of INH resistance. A single M. tuberculosis gene, katG, encoding both catalase and peroxidase, restored sensitivity to INH in a resistant mutant of Mycobacterium smegmatis, and conferred INH susceptibility in some strains of Escherichia coli. Deletion of katG from the chromosome was associated with INH resistance in two patient isolates of M. tuberculosis. 相似文献
190.
W Zhou EA Otto A Cluckey R Airik TW Hurd M Chaki K Diaz FP Lach GR Bennett HY Gee AK Ghosh S Natarajan S Thongthip U Veturi SJ Allen S Janssen G Ramaswami J Dixon F Burkhalter M Spoendlin H Moch MJ Mihatsch J Verine R Reade H Soliman M Godin D Kiss G Monga G Mazzucco K Amann F Artunc RC Newland T Wiech S Zschiedrich TB Huber A Friedl GG Slaats JA Joles R Goldschmeding J Washburn RH Giles S Levy A Smogorzewska F Hildebrandt 《Nature genetics》2012,44(8):910-915
Chronic kidney disease (CKD) represents a major health burden. Its central feature of renal fibrosis is not well understood. By exome sequencing, we identified mutations in FAN1 as a cause of karyomegalic interstitial nephritis (KIN), a disorder that serves as a model for renal fibrosis. Renal histology in KIN is indistinguishable from that of nephronophthisis, except for the presence of karyomegaly. The FAN1 protein has nuclease activity and acts in DNA interstrand cross-link (ICL) repair within the Fanconi anemia DNA damage response (DDR) pathway. We show that cells from individuals with FAN1 mutations have sensitivity to the ICL-inducing agent mitomycin C but do not exhibit chromosome breakage or cell cycle arrest after diepoxybutane treatment, unlike cells from individuals with Fanconi anemia. We complemented ICL sensitivity with wild-type FAN1 but not with cDNA having mutations found in individuals with KIN. Depletion of fan1 in zebrafish caused increased DDR, apoptosis and kidney cysts. Our findings implicate susceptibility to environmental genotoxins and inadequate DNA repair as novel mechanisms contributing to renal fibrosis and CKD. 相似文献