全文获取类型
收费全文 | 92篇 |
免费 | 1篇 |
国内免费 | 2篇 |
专业分类
系统科学 | 4篇 |
理论与方法论 | 1篇 |
现状及发展 | 34篇 |
研究方法 | 11篇 |
综合类 | 45篇 |
出版年
2019年 | 1篇 |
2018年 | 4篇 |
2016年 | 1篇 |
2015年 | 1篇 |
2014年 | 1篇 |
2013年 | 3篇 |
2012年 | 10篇 |
2011年 | 4篇 |
2010年 | 2篇 |
2009年 | 1篇 |
2008年 | 7篇 |
2007年 | 5篇 |
2006年 | 6篇 |
2005年 | 6篇 |
2004年 | 1篇 |
2003年 | 2篇 |
2002年 | 5篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1992年 | 1篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1983年 | 2篇 |
1980年 | 2篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1975年 | 3篇 |
1974年 | 1篇 |
1972年 | 1篇 |
1969年 | 3篇 |
1968年 | 1篇 |
1967年 | 5篇 |
1966年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有95条查询结果,搜索用时 296 毫秒
21.
Characterization of the common genetic defect in humans deficient in debrisoquine metabolism 总被引:53,自引:0,他引:53
F J Gonzalez R C Skoda S Kimura M Umeno U M Zanger D W Nebert H V Gelboin J P Hardwick U A Meyer 《Nature》1988,331(6155):442-446
In population studies of individuals given the antihypertensive drug debrisoquine, two distinct phenotypes have been described: extensive metabolizers excrete 10-200 times more of the urinary metabolite 4-hydroxydebrisoquine than poor metabolizers. In family studies the poor-metabolizer phenotype behaves as an autosomal recessive trait with an incidence between 5% and 10% in the white population of Europe and North America, and extends to the deficient metabolism of more than 20 commonly prescribed drugs. Clinical studies have shown that such individuals are at high risk for the development of adverse side effects from these and probably many other drugs. Here we show that poor metabolizers have negligible amounts of the cytochrome P450 enzyme P450db1. We have cloned the human P450db1 complementary DNA and expressed it in mammalian cell culture. Furthermore, by directly cloning and sequencing cDNAs from several poor-metabolizer livers, we have identified three variant messenger RNAs that are products of mutant genes producing incorrectly spliced db1 pre-mRNA, providing a molecular explanation for one of man's most commonly defective genes (frequency of mutant alleles 35-43%). 相似文献
22.
Gonzalez MR Bischofberger M Pernot L van der Goot FG Frêche B 《Cellular and molecular life sciences : CMLS》2008,65(3):493-507
Pore-forming toxins (PFTs) are the most common class of bacterial protein toxins and constitute important bacterial virulence
factors. The mode of action of PFT is starting to be better understood. In contrast, little is known about the cellular response
to this threat. Recent studies reveal that cells do not just swell and lyse, but are able to sense and react to pore formation,
mount a defense, even repair the damaged membrane and thus survive. These responses involve a variety of signal-transduction
pathways and sophisticated cellular mechanisms such as the pathway regulating lipid metabolism. In this review we discuss
the different classes of bacterial PFTs and their modes of action, and provide examples of how the different bacteria use
PFTs. Finally, we address the more recent field dealing with the eukaryotic cell response to PFT-induced damage.
Received 19 September 2007; received after revision 18 October 2007; accepted 23 October 2007 相似文献
23.
WUSCHEL controls meristem function by direct regulation of cytokinin-inducible response regulators 总被引:2,自引:0,他引:2
Leibfried A To JP Busch W Stehling S Kehle A Demar M Kieber JJ Lohmann JU 《Nature》2005,438(7071):1172-1175
24.
Induction of tumor growth by altered stem-cell asymmetric division in Drosophila melanogaster 总被引:9,自引:0,他引:9
Loss of cell polarity and cancer are tightly correlated, but proof for a causative relationship has remained elusive. In stem cells, loss of polarity and impairment of asymmetric cell division could alter cell fates and thereby render daughter cells unable to respond to the mechanisms that control proliferation. To test this hypothesis, we generated Drosophila melanogaster larval neuroblasts containing mutations in various genes that control asymmetric cell division and then assayed their proliferative potential after transplantation into adult hosts. We found that larval brain tissue carrying neuroblasts with mutations in raps (also called pins), mira, numb or pros grew to more than 100 times their initial size, invading other tissues and killing the hosts in 2 weeks. These tumors became immortal and could be retransplanted into new hosts for years. Six weeks after the first implantation, genome instability and centrosome alterations, two traits of malignant carcinomas, appeared in these tumors. Increasing evidence suggests that some tumors may be of stem cell origin. Our results show that loss of function of any of several genes that control the fate of a stem cell's daughters may result in hyperproliferation, triggering a chain of events that subverts cell homeostasis in a general sense and leads to cancer. 相似文献
25.
A Roseto J P Gonzalez E Edlinger 《Comptes rendus des séances de l'Académie des sciences. Série D, Sciences naturelles》1977,284(22):2307-2308
A simplified method for the diagnosis of Rotavirus by electron microscopy is presented. The incidence of these viruses is observed in new-born infants and the relationship with acute gastroenteritis is recalled. 相似文献
26.
J. Ejden Margarita A. Gonzalez Perez 《Cellular and molecular life sciences : CMLS》1967,23(9):757-758
Resumen Utilizando columna cromatográfica con DEAE-Sephadex A-50 medium, pudimos aislar dos importantes fracciones antigénicas a partir de liquido hidático. Una (IV) con gran actividad en reacción intradermica y otra (VII), altamente purificada con gran actividad en hemaglutinación pasiva. 相似文献
27.
28.
E L Gonzalez 《Nature》1968,219(5151):274-276
29.
The ability of killer T cells carrying the CD8 antigen to detect tumours or intracellular pathogens requires an extensive display of antigenic peptides by major histocompatibility complex (MHC) class I molecules on the surface of potential target cells. These peptides are derived from almost all intracellular proteins and reveal the presence of foreign pathogens and mutations. How cells produce thousands of distinct peptides cleaved to the precise lengths required for binding different MHC class I molecules remains unknown. The peptides are cleaved from endogenously synthesized proteins by the proteasome in the cytoplasm and then trimmed by an unknown aminopeptidase in the endoplasmic reticulum (ER). Here we identify ERAAP, the aminopeptidase associated with antigen processing in the ER. ERAAP has a broad substrate specificity, and its expression is strongly upregulated by interferon-gamma. Reducing the expression of ERAAP through RNA interference prevents the trimming of peptides for MHC class I molecules in the ER and greatly reduces the expression of MHC class I molecules on the cell surface. Thus, ERAAP is the missing link between the products of cytosolic processing and the final peptides presented by MHC class I molecules on the cell surface. 相似文献
30.
TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2 总被引:31,自引:0,他引:31
Pasparakis M Courtois G Hafner M Schmidt-Supprian M Nenci A Toksoy A Krampert M Goebeler M Gillitzer R Israel A Krieg T Rajewsky K Haase I 《Nature》2002,417(6891):861-866
The I kappa B kinase (IKK), consisting of the IKK1 and IKK2 catalytic subunits and the NEMO (also known as IKK gamma) regulatory subunit, phosphorylates I kappa B proteins, targeting them for degradation and thus inducing activation of NF-kappa B (reviewed in refs 1, 2). IKK2 and NEMO are necessary for NF-kappa B activation through pro-inflammatory signals. IKK1 seems to be dispensable for this function but controls epidermal differentiation independently of NF-kappa B. Previous studies suggested that NF-kappa B has a function in the growth regulation of epidermal keratinocytes. Mice lacking RelB or I kappa B alpha, as well as both mice and humans with heterozygous NEMO mutations, develop skin lesions. However, the function of NF-kappa B in the epidermis remains unclear. Here we used Cre/loxP-mediated gene targeting to investigate the function of IKK2 specifically in epidermal keratinocytes. IKK2 deficiency inhibits NF-kappa B activation, but does not lead to cell-autonomous hyperproliferation or impaired differentiation of keratinocytes. Mice with epidermis-specific deletion of IKK2 develop a severe inflammatory skin disease, which is caused by a tumour necrosis factor-mediated, alpha beta T-cell-independent inflammatory response that develops in the skin shortly after birth. Our results suggest that the critical function of IKK2-mediated NF-kappa B activity in epidermal keratinocytes is to regulate mechanisms that maintain the immune homeostasis of the skin. 相似文献