全文获取类型
收费全文 | 976篇 |
免费 | 16篇 |
国内免费 | 15篇 |
专业分类
系统科学 | 21篇 |
丛书文集 | 9篇 |
理论与方法论 | 15篇 |
现状及发展 | 258篇 |
研究方法 | 86篇 |
综合类 | 579篇 |
自然研究 | 39篇 |
出版年
2021年 | 4篇 |
2020年 | 11篇 |
2019年 | 8篇 |
2018年 | 21篇 |
2017年 | 18篇 |
2016年 | 24篇 |
2015年 | 26篇 |
2014年 | 23篇 |
2013年 | 49篇 |
2012年 | 120篇 |
2011年 | 74篇 |
2010年 | 21篇 |
2009年 | 40篇 |
2008年 | 48篇 |
2007年 | 29篇 |
2006年 | 43篇 |
2005年 | 34篇 |
2004年 | 50篇 |
2003年 | 34篇 |
2002年 | 40篇 |
2001年 | 47篇 |
2000年 | 20篇 |
1999年 | 12篇 |
1998年 | 24篇 |
1997年 | 22篇 |
1996年 | 3篇 |
1995年 | 7篇 |
1993年 | 7篇 |
1992年 | 4篇 |
1991年 | 6篇 |
1989年 | 3篇 |
1988年 | 3篇 |
1985年 | 3篇 |
1984年 | 5篇 |
1982年 | 7篇 |
1981年 | 7篇 |
1980年 | 6篇 |
1979年 | 11篇 |
1978年 | 11篇 |
1977年 | 10篇 |
1976年 | 5篇 |
1974年 | 8篇 |
1973年 | 6篇 |
1972年 | 4篇 |
1971年 | 3篇 |
1970年 | 4篇 |
1969年 | 5篇 |
1968年 | 7篇 |
1967年 | 4篇 |
1966年 | 6篇 |
排序方式: 共有1007条查询结果,搜索用时 770 毫秒
51.
Postel-Vinay S Véron AS Tirode F Pierron G Reynaud S Kovar H Oberlin O Lapouble E Ballet S Lucchesi C Kontny U González-Neira A Picci P Alonso J Patino-Garcia A de Paillerets BB Laud K Dina C Froguel P Clavel-Chapelon F Doz F Michon J Chanock SJ Thomas G Cox DG Delattre O 《Nature genetics》2012,44(3):323-327
Ewing sarcoma, a pediatric tumor characterized by EWSR1-ETS fusions, is predominantly observed in populations of European ancestry. We performed a genome-wide association study (GWAS) of 401 French individuals with Ewing sarcoma, 684 unaffected French individuals and 3,668 unaffected individuals of European descent and living in the United States. We identified candidate risk loci at 1p36.22, 10q21 and 15q15. We replicated these loci in two independent sets of cases and controls. Joint analysis identified associations with rs9430161 (P = 1.4 × 10(-20); odds ratio (OR) = 2.2) located 25 kb upstream of TARDBP, rs224278 (P = 4.0 × 10(-17); OR = 1.7) located 5 kb upstream of EGR2 and, to a lesser extent, rs4924410 at 15q15 (P = 6.6 × 10(-9); OR = 1.5). The major risk haplotypes were less prevalent in Africans, suggesting that these loci could contribute to geographical differences in Ewing sarcoma incidence. TARDBP shares structural similarities with EWSR1 and FUS, which encode RNA binding proteins, and EGR2 is a target gene of EWSR1-ETS. Variants at these loci were associated with expression levels of TARDBP, ADO (encoding cysteamine dioxygenase) and EGR2. 相似文献
52.
Purdue MP Johansson M Zelenika D Toro JR Scelo G Moore LE Prokhortchouk E Wu X Kiemeney LA Gaborieau V Jacobs KB Chow WH Zaridze D Matveev V Lubinski J Trubicka J Szeszenia-Dabrowska N Lissowska J Rudnai P Fabianova E Bucur A Bencko V Foretova L Janout V Boffetta P Colt JS Davis FG Schwartz KL Banks RE Selby PJ Harnden P Berg CD Hsing AW Grubb RL Boeing H Vineis P Clavel-Chapelon F Palli D Tumino R Krogh V Panico S Duell EJ Quirós JR Sanchez MJ Navarro C Ardanaz E Dorronsoro M Khaw KT Allen NE 《Nature genetics》2011,43(1):60-65
53.
Garcia-Gonzalo FR Corbit KC Sirerol-Piquer MS Ramaswami G Otto EA Noriega TR Seol AD Robinson JF Bennett CL Josifova DJ García-Verdugo JM Katsanis N Hildebrandt F Reiter JF 《Nature genetics》2011,43(8):776-784
Mutations affecting ciliary components cause ciliopathies. As described here, we investigated Tectonic1 (Tctn1), a regulator of mouse Hedgehog signaling, and found that it is essential for ciliogenesis in some, but not all, tissues. Cell types that do not require Tctn1 for ciliogenesis require it to localize select membrane-associated proteins to the cilium, including Arl13b, AC3, Smoothened and Pkd2. Tctn1 forms a complex with multiple ciliopathy proteins associated with Meckel and Joubert syndromes, including Mks1, Tmem216, Tmem67, Cep290, B9d1, Tctn2 and Cc2d2a. Components of this complex co-localize at the transition zone, a region between the basal body and ciliary axoneme. Like Tctn1, loss of Tctn2, Tmem67 or Cc2d2a causes tissue-specific defects in ciliogenesis and ciliary membrane composition. Consistent with a shared function for complex components, we identified a mutation in TCTN1 that causes Joubert syndrome. Thus, a transition zone complex of Meckel and Joubert syndrome proteins regulates ciliary assembly and trafficking, suggesting that transition zone dysfunction is the cause of these ciliopathies. 相似文献
54.
Gutiérrez-López MD Gilsanz A Yáñez-Mó M Ovalle S Lafuente EM Domínguez C Monk PN González-Alvaro I Sánchez-Madrid F Cabañas C 《Cellular and molecular life sciences : CMLS》2011,68(19):3275-3292
ADAM17/TACE is a metalloproteinase responsible for the shedding of the proinflammatory cytokine TNF-α and many other cell
surface proteins involved in development, cell adhesion, migration, differentiation, and proliferation. Despite the important
biological function of ADAM17, the mechanisms of regulation of its metalloproteinase activity remain largely unknown. We report
here that the tetraspanin CD9 and ADAM17 partially co-localize on the surface of endothelial and monocytic cells. In situ
proximity ligation, co-immunoprecipitation, crosslinking, and pull-down experiments collectively demonstrate a direct association
between these molecules. Functional studies reveal that treatment with CD9-specific antibodies or neoexpression of CD9 exert
negative regulatory effects on ADAM17 sheddase activity. Conversely, CD9 silencing increased the activity of ADAM17 against
its substrates TNF-α and ICAM-1. Taken together, our results show that CD9 associates with ADAM17 and, through this interaction,
negatively regulates the sheddase activity of ADAM17. 相似文献
55.
Rodríguez-Muñoz M Sánchez-Blázquez P Vicente-Sánchez A Bailón C Martín-Aznar B Garzón J 《Cellular and molecular life sciences : CMLS》2011,68(17):2933-2949
A series of pharmacological and physiological studies have demonstrated the functional cross-regulation between MOR and NMDAR.
These receptors coexist at postsynaptic sites in midbrain periaqueductal grey (PAG) neurons, an area implicated in the analgesic
effects of opioids like morphine. In this study, we found that the MOR-associated histidine triad nucleotide-binding protein
1 (HINT1) is essential for maintaining the connection between the NMDAR and MOR. Morphine-induced analgesic tolerance is prevented
and even rescued by inhibiting PKC or by antagonizing NMDAR. However, in the absence of HINT1, the MOR becomes supersensitive
to morphine before suffering a profound and lasting desensitization that is refractory to PKC inhibition or NMDAR antagonism.
Thus, HINT1 emerges as a key protein that is critical for sustaining NMDAR-mediated regulation of MOR signaling strength.
Thus, HINT1 deficiency may contribute to opioid-intractable pain syndromes by causing long-term MOR desensitization via mechanisms
independent of NMDAR. 相似文献
56.
57.
以中国(大陆)为例,把12个公认的城市群空间分布与10大河流流域空间分布叠加,结果表明两点:一是流域与城市群形成了较好的空间对应关系;二是城市群的中心城市一般在流域的最佳区位. 相似文献
58.
This paper describes a distributed estimation scheme (DES) for a bandwidth constrained ad hoc sensor network.The DES is universal in the sense that operations on all sensors are identical and independent of noise distribution.The scheme requires each sensor to transmit just a 1-bit message per observation.Simulation results show that the scheme achieves much better mean-squares error (MSE) performance than the simplified isotropic universal DES and even outperforms the isotropic universal DES which requires more than twice the bandwidth of this scheme. 相似文献
59.
60.