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11.
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
12.
Haigis KM Kendall KR Wang Y Cheung A Haigis MC Glickman JN Niwa-Kawakita M Sweet-Cordero A Sebolt-Leopold J Shannon KM Settleman J Giovannini M Jacks T 《Nature genetics》2008,40(5):600-608
Kras is commonly mutated in colon cancers, but mutations in Nras are rare. We have used genetically engineered mice to determine whether and how these related oncogenes regulate homeostasis and tumorigenesis in the colon. Expression of K-Ras(G12D) in the colonic epithelium stimulated hyperproliferation in a Mek-dependent manner. N-Ras(G12D) did not alter the growth properties of the epithelium, but was able to confer resistance to apoptosis. In the context of an Apc-mutant colonic tumor, activation of K-Ras led to defects in terminal differentiation and expansion of putative stem cells within the tumor epithelium. This K-Ras tumor phenotype was associated with attenuated signaling through the MAPK pathway, and human colon cancer cells expressing mutant K-Ras were hypersensitive to inhibition of Raf, but not Mek. These studies demonstrate clear phenotypic differences between mutant Kras and Nras, and suggest that the oncogenic phenotype of mutant K-Ras might be mediated by noncanonical signaling through Ras effector pathways. 相似文献
13.
Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis 总被引:21,自引:0,他引:21
Palmer CN Irvine AD Terron-Kwiatkowski A Zhao Y Liao H Lee SP Goudie DR Sandilands A Campbell LE Smith FJ O'Regan GM Watson RM Cecil JE Bale SJ Compton JG DiGiovanna JJ Fleckman P Lewis-Jones S Arseculeratne G Sergeant A Munro CS El Houate B McElreavey K Halkjaer LB Bisgaard H Mukhopadhyay S McLean WH 《Nature genetics》2006,38(4):441-446
Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades and now affects approximately 20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable. Although most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated. Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Here we show that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis. These variants are carried by approximately 9% of people of European origin. These variants also show highly significant association with asthma occurring in the context of atopic dermatitis. This work establishes a key role for impaired skin barrier function in the development of atopic disease. 相似文献
14.
Kraytsberg Y Kudryavtseva E McKee AC Geula C Kowall NW Khrapko K 《Nature genetics》2006,38(5):518-520
Using a novel single-molecule PCR approach to quantify the total burden of mitochondrial DNA (mtDNA) molecules with deletions, we show that a high proportion of individual pigmented neurons in the aged human substantia nigra contain very high levels of mtDNA deletions. Molecules with deletions are largely clonal within each neuron; that is, they originate from a single deleted mtDNA molecule that has expanded clonally. The fraction of mtDNA deletions is significantly higher in cytochrome c oxidase (COX)-deficient neurons than in COX-positive neurons, suggesting that mtDNA deletions may be directly responsible for impaired cellular respiration. 相似文献
15.
The genetic basis of most conditions characterized by congenital contractures is largely unknown. Here we show that mutations in the embryonic myosin heavy chain (MYH3) gene cause Freeman-Sheldon syndrome (FSS), one of the most severe multiple congenital contracture (that is, arthrogryposis) syndromes, and nearly one-third of all cases of Sheldon-Hall syndrome (SHS), the most common distal arthrogryposis. FSS and SHS mutations affect different myosin residues, demonstrating that MYH3 genotype is predictive of phenotype. A structure-function analysis shows that nearly all of the MYH3 mutations are predicted to interfere with myosin's catalytic activity. These results add to the growing body of evidence showing that congenital contractures are a shared outcome of prenatal defects in myofiber force production. Elucidation of the genetic basis of these syndromes redefines congenital contractures as unique defects of the sarcomere and provides insights about what has heretofore been a poorly understood group of disorders. 相似文献
16.
20世纪50年代集体化改革之前小凉山奴隶制度特有的社会经济进程表明,诺苏社会曾是一个拥有奴隶的社会,但它并不是奴隶社会。该结论基于其他关于奴隶制研究中的传统观念即在奴隶社会中奴隶制是体系得以维持的关键所在。1956年之前,小凉山的生产目的是生计而不是市场。此外,小凉山的精英阶层更依赖于系谱或继嗣,而不是财富;另一个相关论点是,在诺苏身份和认同的决定中,亲属比等级发挥了更为基础的作用。 相似文献
17.
Summary Melatonin, in concentrations up to 10–3
M, showed no effect on mitosis in cultures of HeLa or KB cells. However, when melatonin at 10–4
M was preincubated with HeLa cells prior to addition of 10–7
M colchicine, a reduction in the mitotic index, in comparison to colchicine alone, was observed.This work was supported by PHS Grant No. CA 16425. 相似文献
18.
R. A. Buckland Judith M. Fletcher Ann C. Chandley 《Cellular and molecular life sciences : CMLS》1976,32(9):1146-1149
Summary Giemsa banding techniques have been used to identify the chromosomes of the domestic horse. 相似文献
19.
Shiva M. Singh Caroline H. Wang Ann Phillips 《Cellular and molecular life sciences : CMLS》1982,38(12):1487-1489
Summary The genotype difference (dystrophic vs nondystrophic) in the LDH isozymes is observed in kidney. These differences are evident only at birth and at early developmental stages (before the expression of dystrophic symptoms). The tissue specific genotype differences for PK are limited to the thigh muscle (M form) and heart (L form), after the onset of the condition. These differences may reflect the pleiotropic effect of the dy2J locus during the temporal regulation of these and other enzymes implicated in muscular dystrophy (MD).This research was financed by a Natural Sciences and Engineering Research Council Canada grant to S.M.S. 相似文献
20.
Zusammenfassung Im Rahmen eines heuristischen Modells und unter dem Einfluss der psychoanaleptischen Drogc Psilocybin wird die regulierend-complementierende geistige Tätigkeit untersucht. Gesunde, junge Volontäre vermögen nach oraler Verabreichung von 10–12 mg Psilocybin gedruckte Texte zu lesen, obgleich der obere Teil jeder Zeile bis zu 74% unsichtbar ist. 相似文献