全文获取类型
收费全文 | 304篇 |
免费 | 1篇 |
国内免费 | 1篇 |
专业分类
系统科学 | 5篇 |
教育与普及 | 1篇 |
理论与方法论 | 7篇 |
现状及发展 | 114篇 |
研究方法 | 48篇 |
综合类 | 130篇 |
自然研究 | 1篇 |
出版年
2020年 | 2篇 |
2018年 | 4篇 |
2017年 | 2篇 |
2016年 | 4篇 |
2015年 | 5篇 |
2014年 | 3篇 |
2013年 | 5篇 |
2012年 | 28篇 |
2011年 | 22篇 |
2010年 | 8篇 |
2008年 | 19篇 |
2007年 | 16篇 |
2006年 | 22篇 |
2005年 | 21篇 |
2004年 | 27篇 |
2003年 | 11篇 |
2002年 | 7篇 |
2001年 | 4篇 |
2000年 | 7篇 |
1999年 | 6篇 |
1998年 | 6篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1990年 | 2篇 |
1988年 | 3篇 |
1985年 | 5篇 |
1984年 | 2篇 |
1982年 | 1篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1973年 | 1篇 |
1972年 | 3篇 |
1971年 | 10篇 |
1970年 | 4篇 |
1969年 | 3篇 |
1968年 | 1篇 |
1967年 | 4篇 |
1966年 | 2篇 |
1965年 | 1篇 |
1964年 | 1篇 |
1960年 | 2篇 |
1948年 | 2篇 |
1947年 | 2篇 |
1946年 | 1篇 |
1945年 | 1篇 |
排序方式: 共有306条查询结果,搜索用时 31 毫秒
101.
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
102.
Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease 总被引:2,自引:0,他引:2
Barrett JC Hansoul S Nicolae DL Cho JH Duerr RH Rioux JD Brant SR Silverberg MS Taylor KD Barmada MM Bitton A Dassopoulos T Datta LW Green T Griffiths AM Kistner EO Murtha MT Regueiro MD Rotter JI Schumm LP Steinhart AH Targan SR Xavier RJ;NIDDK IBD Genetics Consortium Libioulle C Sandor C Lathrop M Belaiche J Dewit O Gut I Heath S Laukens D Mni M Rutgeerts P Van Gossum A Zelenika D Franchimont D Hugot JP de Vos M Vermeire S 《Nature genetics》2008,40(8):955-962
Several risk factors for Crohn's disease have been identified in recent genome-wide association studies. To advance gene discovery further, we combined data from three studies on Crohn's disease (a total of 3,230 cases and 4,829 controls) and carried out replication in 3,664 independent cases with a mixture of population-based and family-based controls. The results strongly confirm 11 previously reported loci and provide genome-wide significant evidence for 21 additional loci, including the regions containing STAT3, JAK2, ICOSLG, CDKAL1 and ITLN1. The expanded molecular understanding of the basis of this disease offers promise for informed therapeutic development. 相似文献
103.
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
104.
105.
Dibbens LM Tarpey PS Hynes K Bayly MA Scheffer IE Smith R Bomar J Sutton E Vandeleur L Shoubridge C Edkins S Turner SJ Stevens C O'Meara S Tofts C Barthorpe S Buck G Cole J Halliday K Jones D Lee R Madison M Mironenko T Varian J West S Widaa S Wray P Teague J Dicks E Butler A Menzies A Jenkinson A Shepherd R Gusella JF Afawi Z Mazarib A Neufeld MY Kivity S Lev D Lerman-Sagie T Korczyn AD Derry CP Sutherland GR Friend K Shaw M Corbett M Kim HG Geschwind DH Thomas P Haan E Ryan S McKee S 《Nature genetics》2008,40(6):776-781
Epilepsy and mental retardation limited to females (EFMR) is a disorder with an X-linked mode of inheritance and an unusual expression pattern. Disorders arising from mutations on the X chromosome are typically characterized by affected males and unaffected carrier females. In contrast, EFMR spares transmitting males and affects only carrier females. Aided by systematic resequencing of 737 X chromosome genes, we identified different protocadherin 19 (PCDH19) gene mutations in seven families with EFMR. Five mutations resulted in the introduction of a premature termination codon. Study of two of these demonstrated nonsense-mediated decay of PCDH19 mRNA. The two missense mutations were predicted to affect adhesiveness of PCDH19 through impaired calcium binding. PCDH19 is expressed in developing brains of human and mouse and is the first member of the cadherin superfamily to be directly implicated in epilepsy or mental retardation. 相似文献
106.
Charlier C Coppieters W Rollin F Desmecht D Agerholm JS Cambisano N Carta E Dardano S Dive M Fasquelle C Frennet JC Hanset R Hubin X Jorgensen C Karim L Kent M Harvey K Pearce BR Simon P Tama N Nie H Vandeputte S Lien S Longeri M Fredholm M Harvey RJ Georges M 《Nature genetics》2008,40(4):449-454
The widespread use of elite sires by means of artificial insemination in livestock breeding leads to the frequent emergence of recessive genetic defects, which cause significant economic and animal welfare concerns. Here we show that the availability of genome-wide, high-density SNP panels, combined with the typical structure of livestock populations, markedly accelerates the positional identification of genes and mutations that cause inherited defects. We report the fine-scale mapping of five recessive disorders in cattle and the molecular basis for three of these: congenital muscular dystony (CMD) types 1 and 2 in Belgian Blue cattle and ichthyosis fetalis in Italian Chianina cattle. Identification of these causative mutations has an immediate translation into breeding practice, allowing marker assisted selection against the defects through avoidance of at-risk matings. 相似文献
107.
Meriem El Ghachi Nicole Howe Rodolphe Auger Alexandre Lambion Annick Guiseppi François Delbrassine Guillaume Manat Sophie Roure Sabine Peslier Eric Sauvage Lutz Vogeley Juan-Carlos Rengifo-Gonzalez Paulette Charlier Dominique Mengin-Lecreulx Maryline Foglino Thierry Touzé Martin Caffrey Frédéric Kerff 《Cellular and molecular life sciences : CMLS》2017,74(12):2319-2332
Type 2 phosphatidic acid phosphatases (PAP2s) can be either soluble or integral membrane enzymes. In bacteria, integral membrane PAP2s play major roles in the metabolisms of glycerophospholipids, undecaprenyl-phosphate (C55-P) lipid carrier and lipopolysaccharides. By in vivo functional experiments and biochemical characterization we show that the membrane PAP2 coded by the Bacillus subtilis yodM gene is the principal phosphatidylglycerol phosphate (PGP) phosphatase of B. subtilis. We also confirm that this enzyme, renamed bsPgpB, has a weaker activity on C55-PP. Moreover, we solved the crystal structure of bsPgpB at 2.25 Å resolution, with tungstate (a phosphate analog) in the active site. The structure reveals two lipid chains in the active site vicinity, allowing for PGP substrate modeling and molecular dynamic simulation. Site-directed mutagenesis confirmed the residues important for substrate specificity, providing a basis for predicting the lipids preferentially dephosphorylated by membrane PAP2s. 相似文献
108.
Jacques Dutka 《Archive for History of Exact Sciences》1991,43(3):225-249
Communicated by U. Bottazzini 相似文献
109.
The rapid closure of the Venus flytrap (Dionaea muscipula) leaf in about 100 ms is one of the fastest movements in the plant kingdom. This led Darwin to describe the plant as "one of the most wonderful in the world". The trap closure is initiated by the mechanical stimulation of trigger hairs. Previous studies have focused on the biochemical response of the trigger hairs to stimuli and quantified the propagation of action potentials in the leaves. Here we complement these studies by considering the post-stimulation mechanical aspects of Venus flytrap closure. Using high-speed video imaging, non-invasive microscopy techniques and a simple theoretical model, we show that the fast closure of the trap results from a snap-buckling instability, the onset of which is controlled actively by the plant. Our study identifies an ingenious solution to scaling up movements in non-muscular engines and provides a general framework for understanding nastic motion in plants. 相似文献
110.
Gribouval O Gonzales M Neuhaus T Aziza J Bieth E Laurent N Bouton JM Feuillet F Makni S Ben Amar H Laube G Delezoide AL Bouvier R Dijoud F Ollagnon-Roman E Roume J Joubert M Antignac C Gubler MC 《Nature genetics》2005,37(9):964-968
Autosomal recessive renal tubular dysgenesis is a severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (Potter phenotype). Absence or paucity of differentiated proximal tubules is the histopathological hallmark of the disease and may be associated with skull ossification defects. We studied 11 individuals with renal tubular dysgenesis, belonging to nine families, and found that they had homozygous or compound heterozygous mutations in the genes encoding renin, angiotensinogen, angiotensin converting enzyme or angiotensin II receptor type 1. We propose that renal lesions and early anuria result from chronic low perfusion pressure of the fetal kidney, a consequence of renin-angiotensin system inactivity. This is the first identification to our knowledge of a renal mendelian disorder linked to genetic defects in the renin-angiotensin system, highlighting the crucial role of the renin-angiotensin system in human kidney development. 相似文献