全文获取类型
收费全文 | 353篇 |
免费 | 0篇 |
国内免费 | 1篇 |
专业分类
丛书文集 | 2篇 |
教育与普及 | 2篇 |
现状及发展 | 80篇 |
研究方法 | 43篇 |
综合类 | 211篇 |
自然研究 | 16篇 |
出版年
2020年 | 1篇 |
2018年 | 2篇 |
2017年 | 2篇 |
2015年 | 1篇 |
2014年 | 1篇 |
2013年 | 2篇 |
2012年 | 9篇 |
2011年 | 33篇 |
2010年 | 2篇 |
2009年 | 1篇 |
2008年 | 12篇 |
2007年 | 10篇 |
2006年 | 16篇 |
2005年 | 11篇 |
2004年 | 6篇 |
2003年 | 8篇 |
2002年 | 25篇 |
2001年 | 21篇 |
2000年 | 24篇 |
1999年 | 14篇 |
1992年 | 7篇 |
1991年 | 1篇 |
1990年 | 5篇 |
1989年 | 2篇 |
1988年 | 5篇 |
1987年 | 12篇 |
1986年 | 2篇 |
1985年 | 7篇 |
1984年 | 7篇 |
1982年 | 7篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1979年 | 5篇 |
1978年 | 7篇 |
1977年 | 2篇 |
1976年 | 6篇 |
1975年 | 3篇 |
1974年 | 6篇 |
1973年 | 7篇 |
1972年 | 7篇 |
1971年 | 5篇 |
1970年 | 12篇 |
1969年 | 9篇 |
1968年 | 3篇 |
1967年 | 5篇 |
1966年 | 6篇 |
1965年 | 4篇 |
1964年 | 3篇 |
1962年 | 2篇 |
1959年 | 2篇 |
排序方式: 共有354条查询结果,搜索用时 31 毫秒
91.
Danielle Kamato Partha Mitra Felicity Davis Narin Osman Rebecca Chaplin Peter J. Cabot Rizwana Afroz Walter Thomas Wenhua Zheng Harveen Kaur Margaret Brimble Peter J. Little 《Cellular and molecular life sciences : CMLS》2017,74(8):1379-1390
Seven transmembrane G protein-coupled receptors (GPCRs) have gained much interest in recent years as it is the largest class among cell surface receptors. G proteins lie in the heart of GPCRs signalling and therefore can be therapeutically targeted to overcome complexities in GPCR responses and signalling. G proteins are classified into four families (Gi, Gs, G12/13 and Gq); Gq is further subdivided into four classes. Among them Gαq and Gαq/11 isoforms are most crucial and ubiquitously expressed; these isoforms are almost 88% similar at their amino acid sequence but may exhibit functional divergences. However, uncertainties often arise about Gαq and Gαq/11 inhibitors, these G proteins might also have suitability to the invention of novel-specific inhibitors for each isoforms. YM-254890 and UBO-QIC are discovered as potent inhibitors of Gαq functions and also investigated in thrombin protease-activated receptor (PAR)-1 inhibitors and platelet aggregation inhibition. The most likely G protein involved in PAR-1 stimulates responses is one of the Gαq family isoforms. In this review, we highlight the molecular structures and pharmacological responses of Gαq family which may reflect the biochemical and molecular role of Gαq and Gαq/11. The advanced understanding of Gαq and Gαq/11 role in GPCR signalling may shed light on our understanding on cell biology, cellular physiology and pathophysiology and also lead to the development of novel therapeutic agents for a number of diseases. 相似文献
92.
Frøkjaer-Jensen C Davis MW Hopkins CE Newman BJ Thummel JM Olesen SP Grunnet M Jorgensen EM 《Nature genetics》2008,40(11):1375-1383
At present, transgenes in Caenorhabditis elegans are generated by injecting DNA into the germline. The DNA assembles into a semistable extrachromosomal array composed of many copies of injected DNA. These transgenes are typically overexpressed in somatic cells and silenced in the germline. We have developed a method that inserts a single copy of a transgene into a defined site. Mobilization of a Mos1 transposon generates a double-strand break in noncoding DNA. The break is repaired by copying DNA from an extrachromosomal template into the chromosomal site. Homozygous single-copy insertions can be obtained in less than 2 weeks by injecting approximately 20 worms. We have successfully inserted transgenes as long as 9 kb and verified that single copies are inserted at the targeted site. Single-copy transgenes are expressed at endogenous levels and can be expressed in the female and male germlines. 相似文献
93.
94.
40年前A.爱因斯坦给M.玻恩的一封信中写道,“上帝不玩骰子。”爱因斯坦是始终反对量子论的概率解释的,他不倦地探索着与经典力学更为直接的类比,即考虑没有概率不定性的确定过程。如今,40年过去了,没有人会惊讶:甚至在一个经典哈密顿动力系统中也存在着(chas)在物理客体规则运动的领域内,在没有人预期会有的地方冒出 相似文献
95.
The genome of the social amoeba Dictyostelium discoideum 总被引:2,自引:0,他引:2
Eichinger L Pachebat JA Glöckner G Rajandream MA Sucgang R Berriman M Song J Olsen R Szafranski K Xu Q Tunggal B Kummerfeld S Madera M Konfortov BA Rivero F Bankier AT Lehmann R Hamlin N Davies R Gaudet P Fey P Pilcher K Chen G Saunders D Sodergren E Davis P Kerhornou A Nie X Hall N Anjard C Hemphill L Bason N Farbrother P Desany B Just E Morio T Rost R Churcher C Cooper J Haydock S van Driessche N Cronin A Goodhead I Muzny D Mourier T Pain A Lu M Harper D Lindsay R Hauser H James K Quiles M 《Nature》2005,435(7038):43-57
The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi. 相似文献
96.
97.
Teraishi F Wu S Sasaki J Zhang L Davis JJ Guo W Dong F Fang B 《Cellular and molecular life sciences : CMLS》2005,62(19-20):2382-2389
We recently identified two thiazolidin compounds, 5-[(4-methylphenyl)methylene]-2-(phenylamino)-4(5H)-thiazolone (MMPT) and 5-(2,4-dihydroxybenzylidene)-2-(phenylimino)-1,3-thiazolidin (DBPT), that inhibit the growth of human non-small-cell lung and colon cancer cells independent of P-glycoprotein and p53 status. Here we further investigated the mechanism by which these thiazolidin compounds mediate their anticancer effects. Treatment of cancer cells with MMPT and DBPT led to a time-dependent accumulation of cells arrested in the G2/M phase with modulation of the expression of proteins such as cyclin B1, cdc25C, and phosphorylated histone H3. Moreover, treatment with MMPT and DBPT increased M-phase arrest with abnormal spindle formation. DBPT-mediated G2/M phase arrest and phosphorylation of cdc25C and histone H3 were abrogated when JNK activation was blocked either with SP600125, a specific JNK inhibitor, or a dominant-negative JNK1 gene. Moreover, DBPT-mediated microtubule disruption was also blocked by SP600125 treatment. Our results demonstrate that thiazolidin compounds can effectively induce G2/M arrest in cancer cells and that this G2/M arrest requires JNK activation. 相似文献
98.
Maternal effect of Hsf1 on reproductive success 总被引:17,自引:0,他引:17
99.
Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling 总被引:366,自引:0,他引:366
Alizadeh AA Eisen MB Davis RE Ma C Lossos IS Rosenwald A Boldrick JC Sabet H Tran T Yu X Powell JI Yang L Marti GE Moore T Hudson J Lu L Lewis DB Tibshirani R Sherlock G Chan WC Greiner TC Weisenburger DD Armitage JO Warnke R Levy R Wilson W Grever MR Byrd JC Botstein D Brown PO Staudt LM 《Nature》2000,403(6769):503-511
Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, is clinically heterogeneous: 40% of patients respond well to current therapy and have prolonged survival, whereas the remainder succumb to the disease. We proposed that this variability in natural history reflects unrecognized molecular heterogeneity in the tumours. Using DNA microarrays, we have conducted a systematic characterization of gene expression in B-cell malignancies. Here we show that there is diversity in gene expression among the tumours of DLBCL patients, apparently reflecting the variation in tumour proliferation rate, host response and differentiation state of the tumour. We identified two molecularly distinct forms of DLBCL which had gene expression patterns indicative of different stages of B-cell differentiation. One type expressed genes characteristic of germinal centre B cells ('germinal centre B-like DLBCL'); the second type expressed genes normally induced during in vitro activation of peripheral blood B cells ('activated B-like DLBCL'). Patients with germinal centre B-like DLBCL had a significantly better overall survival than those with activated B-like DLBCL. The molecular classification of tumours on the basis of gene expression can thus identify previously undetected and clinically significant subtypes of cancer. 相似文献
100.
A central control for cell growth 总被引:4,自引:0,他引:4