全文获取类型
收费全文 | 323篇 |
免费 | 0篇 |
国内免费 | 1篇 |
专业分类
系统科学 | 4篇 |
教育与普及 | 1篇 |
现状及发展 | 46篇 |
研究方法 | 102篇 |
综合类 | 164篇 |
自然研究 | 7篇 |
出版年
2021年 | 4篇 |
2020年 | 1篇 |
2018年 | 7篇 |
2017年 | 6篇 |
2016年 | 3篇 |
2015年 | 2篇 |
2013年 | 5篇 |
2012年 | 41篇 |
2011年 | 49篇 |
2010年 | 14篇 |
2009年 | 2篇 |
2008年 | 23篇 |
2007年 | 31篇 |
2006年 | 34篇 |
2005年 | 30篇 |
2004年 | 23篇 |
2003年 | 19篇 |
2002年 | 23篇 |
1976年 | 1篇 |
1972年 | 2篇 |
1971年 | 1篇 |
1968年 | 1篇 |
1957年 | 1篇 |
1955年 | 1篇 |
排序方式: 共有324条查询结果,搜索用时 15 毫秒
71.
Vitart V Rudan I Hayward C Gray NK Floyd J Palmer CN Knott SA Kolcic I Polasek O Graessler J Wilson JF Marinaki A Riches PL Shu X Janicijevic B Smolej-Narancic N Gorgoni B Morgan J Campbell S Biloglav Z Barac-Lauc L Pericic M Klaric IM Zgaga L Skaric-Juric T Wild SH Richardson WA Hohenstein P Kimber CH Tenesa A Donnelly LA Fairbanks LD Aringer M McKeigue PM Ralston SH Morris AD Rudan P Hastie ND Campbell H Wright AF 《Nature genetics》2008,40(4):437-442
Uric acid is the end product of purine metabolism in humans and great apes, which have lost hepatic uricase activity, leading to uniquely high serum uric acid concentrations (200-500 microM) compared with other mammals (3-120 microM). About 70% of daily urate disposal occurs via the kidneys, and in 5-25% of the human population, impaired renal excretion leads to hyperuricemia. About 10% of people with hyperuricemia develop gout, an inflammatory arthritis that results from deposition of monosodium urate crystals in the joint. We have identified genetic variants within a transporter gene, SLC2A9, that explain 1.7-5.3% of the variance in serum uric acid concentrations, following a genome-wide association scan in a Croatian population sample. SLC2A9 variants were also associated with low fractional excretion of uric acid and/or gout in UK, Croatian and German population samples. SLC2A9 is a known fructose transporter, and we now show that it has strong uric acid transport activity in Xenopus laevis oocytes. 相似文献
72.
Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants 总被引:2,自引:0,他引:2
Wellcome Trust Case Control Consortium;Australo-Anglo-American Spondylitis Consortium 《Nature genetics》2007,39(11):1329-1337
We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases. 相似文献
73.
74.
Liu F Thirumangalathu S Gallant NM Yang SH Stoick-Cooper CL Reddy ST Andl T Taketo MM Dlugosz AA Moon RT Barlow LA Millar SE 《Nature genetics》2007,39(1):106-112
Fungiform taste papillae form a regular array on the dorsal tongue. Taste buds arise from papilla epithelium and, unusually for epithelial derivatives, synapse with neurons, release neurotransmitters and generate receptor and action potentials. Despite the importance of taste as one of our five senses, genetic analyses of taste papilla and bud development are lacking. We demonstrate that Wnt-beta-catenin signaling is activated in developing fungiform placodes and taste bud cells. A dominant stabilizing mutation of epithelial beta-catenin causes massive overproduction of enlarged fungiform papillae and taste buds. Likewise, genetic deletion of epithelial beta-catenin or inhibition of Wnt-beta-catenin signaling by ectopic dickkopf1 (Dkk1) blocks initiation of fungiform papilla morphogenesis. Ectopic papillae are innervated in the stabilizing beta-catenin mutant, whereas ectopic Dkk1 causes absence of lingual epithelial innervation. Thus, Wnt-beta-catenin signaling is critical for fungiform papilla and taste bud development. Altered regulation of this pathway may underlie evolutionary changes in taste papilla patterning. 相似文献
75.
Anika M. Helferich Sarah J. Brockmann Jörg Reinders Dhruva Deshpande Karlheinz Holzmann David Brenner Peter M. Andersen Susanne Petri Dietmar R. Thal Jens Michaelis Markus Otto Steffen Just Albert C. Ludolph Karin M. Danzer Axel Freischmidt Jochen H. Weishaupt 《Cellular and molecular life sciences : CMLS》2018,75(23):4301-4319
76.
Sarah S. Richardson 《Studies in history and philosophy of science》2009,40(1):14-24
Recent scholarship resuscitates the history and philosophy of a ‘left wing’ in the Vienna Circle, offering a counterhistory to the conventional image of analytic philosophy as politically conformist. This paper disputes the historical claim that early logical empiricists developed a political philosophy of science. Though some individuals in the Vienna Circle, including Rudolf Carnap and Otto Neurath, believed strongly in the importance of science to social progress, they did not construct a political philosophy of science. Both Carnap and Neurath were committed to forms of political neutralism that run strongly against a political reading of their logical empiricism. In addition, Carnap and Neurath sharply differ on precisely the subject of the place of politics in logical empiricism, throwing into question the construct of the ‘Left Vienna Circle’ as a coherent, sociohistorical, programmatic unit within the Vienna Circle. 相似文献
77.
Thirty-five study sites were established in the meadow communities surrounding Utah Lake in central Utah. The study sites ranged across several community types. Glaux maritima was found in all sites but varied as to its ecological importance in these communities. Sixteen soil factors were measured relative to the stands studied. Cover of Glaux maritima correlated with parts per million sodium and total soluble salts in the soil. No other factors correlated significantly with the cover of Glaux maritima. Glaux maritima occupied only those sites with high levels of moisture throughout the growing season. The high moisture levels came from springs, seeps, elevated water tables, and early seasonal inundation. High levels of Glaux maritima cover corresponded to low numbers of species in the habitat. 相似文献
78.
Laurie NA Donovan SL Shih CS Zhang J Mills N Fuller C Teunisse A Lam S Ramos Y Mohan A Johnson D Wilson M Rodriguez-Galindo C Quarto M Francoz S Mendrysa SM Guy RK Marine JC Jochemsen AG Dyer MA 《Nature》2006,444(7115):61-66
Most human tumours have genetic mutations in their Rb and p53 pathways, but retinoblastoma is thought to be an exception. Studies suggest that retinoblastomas, which initiate with mutations in the gene retinoblastoma 1 (RB1), bypass the p53 pathway because they arise from intrinsically death-resistant cells during retinal development. In contrast to this prevailing theory, here we show that the tumour surveillance pathway mediated by Arf, MDM2, MDMX and p53 is activated after loss of RB1 during retinogenesis. RB1-deficient retinoblasts undergo p53-mediated apoptosis and exit the cell cycle. Subsequently, amplification of the MDMX gene and increased expression of MDMX protein are strongly selected for during tumour progression as a mechanism to suppress the p53 response in RB1-deficient retinal cells. Our data provide evidence that the p53 pathway is inactivated in retinoblastoma and that this cancer does not originate from intrinsically death-resistant cells as previously thought. In addition, they support the idea that MDMX is a specific chemotherapeutic target for treating retinoblastoma. 相似文献
79.
80.