全文获取类型
收费全文 | 550篇 |
免费 | 99篇 |
国内免费 | 1篇 |
出版年
2021年 | 11篇 |
2020年 | 5篇 |
2019年 | 5篇 |
2018年 | 11篇 |
2017年 | 9篇 |
2016年 | 14篇 |
2015年 | 13篇 |
2014年 | 19篇 |
2013年 | 19篇 |
2012年 | 44篇 |
2011年 | 31篇 |
2010年 | 37篇 |
2009年 | 21篇 |
2008年 | 23篇 |
2007年 | 29篇 |
2006年 | 21篇 |
2005年 | 23篇 |
2004年 | 22篇 |
2003年 | 19篇 |
2002年 | 19篇 |
2001年 | 12篇 |
2000年 | 16篇 |
1999年 | 7篇 |
1998年 | 13篇 |
1997年 | 9篇 |
1996年 | 9篇 |
1994年 | 6篇 |
1993年 | 3篇 |
1992年 | 4篇 |
1991年 | 8篇 |
1990年 | 6篇 |
1989年 | 7篇 |
1988年 | 7篇 |
1987年 | 11篇 |
1986年 | 6篇 |
1985年 | 8篇 |
1984年 | 10篇 |
1983年 | 8篇 |
1982年 | 3篇 |
1980年 | 5篇 |
1977年 | 5篇 |
1976年 | 13篇 |
1975年 | 6篇 |
1974年 | 5篇 |
1973年 | 9篇 |
1971年 | 4篇 |
1970年 | 7篇 |
1969年 | 4篇 |
1968年 | 5篇 |
1942年 | 3篇 |
排序方式: 共有650条查询结果,搜索用时 281 毫秒
581.
Schilte C Buckwalter MR Laird ME Diamond MS Schwartz O Albert ML 《Journal of immunology (Baltimore, Md. : 1950)》2012,188(7):2967-2971
The host response to Chikungunya virus is dependent on the direct action of type I IFN on infected nonhematopoietic cells. Prior studies have demonstrated that multiple host sensors coordinate an antiviral response; however, the tissue source(s) and signaling pathways for IFN production remain unknown. In this study, we demonstrate that IRF-3 and IRF-7 are functionally redundant, but lack of both factors results in lethal infection in adult mice. Reciprocal bone marrow chimeras indicated that IRF-3 or IRF-7 expression in either hematopoietic or nonhemotopoietic cell compartments was capable of inducing an antiviral response. Interestingly, redundancy of IRF-3 and IRF-7 was age dependent, as neonatal animals lacking either factor succumbed to infection. We further demonstrate that IPS-1 is essential in nonhematopoietic cells and preferentially required during early life. These results highlight the interplay between nonimmune and immune cells during Chikungunya virus infection and suggest an important role for nonhematopoietic cells as a critical source of IFN-α/β. 相似文献
582.
Saczewski J Hudson A Scheinin M Rybczynska A Ma D Saczewski F Laird S Laurila JM Boblewski K Lehmann A Gu J Watts H 《Bioorganic & medicinal chemistry》2012,20(1):108-116
A series of 2-[(heteroaryl)methyl]imidazolines was synthesized and tested for their activities at α(1)- and α(2)-adrenoceptors and imidazoline I(1) and I(2) receptors. The most active 2-[(indazol-1-yl)methyl]imidazolines showed high or moderate affinities for α(1)- and α(2)-adrenoceptors. However, their intrinsic activities at α(2A)-adrenoceptors proved to be negligible. A selected 7-chloro derivative behaved as a potent α(1)-adrenoceptor antagonist and exhibited peripherally mediated hypotensive effects in rats. 相似文献
583.
584.
585.
Nunzia D'Urzo Manuele Martinelli Alfredo Pezzicoli Virginia De Cesare Vittoria Pinto Immaculada Margarit John Laird Telford Domenico Maione 《Applied and environmental microbiology》2014,80(7):2176-2185
Streptococcus agalactiae, also known as group B Streptococcus (GBS), is a primary colonizer of the anogenital mucosa of up to 40% of healthy women and an important cause of invasive neonatal infections worldwide. Among the 10 known capsular serotypes, GBS type III accounts for 30 to 76% of the cases of neonatal meningitis. In recent years, the ability of GBS to form biofilm attracted attention for its possible role in fitness and virulence. Here, a new in vitro biofilm formation protocol was developed to guarantee more stringent conditions, to better discriminate between strong-, low-, and non-biofilm-forming strains, and to facilitate interpretation of data. This protocol was used to screen the biofilm-forming abilities of 366 GBS clinical isolates from pregnant women and from neonatal infections of different serotypes in relation to medium composition and pH. The results identified a subset of isolates of serotypes III and V that formed strong biofilms under acidic conditions. Importantly, the best biofilm formers belonged to serotype III hypervirulent clone ST-17. Moreover, the abilities of proteinase K to strongly inhibit biofilm formation and to disaggregate mature biofilms suggested that proteins play an essential role in promoting GBS biofilm initiation and contribute to biofilm structural stability. 相似文献
586.
Both population-based and family-based designs are commonly used in genetic association studies to locate genes that underlie complex diseases. The simplest version of the family-based design--the transmission disequilibrium test--is well known, but the numerous extensions that broaden its scope and power are less widely appreciated. Family-based designs have unique advantages over population-based designs, as they are robust against population admixture and stratification, allow both linkage and association to be tested for and offer a solution to the problem of model building. Furthermore, the fact that family-based designs contain both within- and between-family information has substantial benefits in terms of multiple-hypothesis testing, especially in the context of whole-genome association studies. 相似文献
587.
Debra L Fulton Yvonne Y Li Matthew R Laird Benjamin GS Horsman Fiona M Roche Fiona SL Brinkman 《BMC bioinformatics》2006,7(1):270-16
Background
Orthologs (genes that have diverged after a speciation event) tend to have similar function, and so their prediction has become an important component of comparative genomics and genome annotation. The gold standard phylogenetic analysis approach of comparing available organismal phylogeny to gene phylogeny is not easily automated for genome-wide analysis; therefore, ortholog prediction for large genome-scale datasets is typically performed using a reciprocal-best-BLAST-hits (RBH) approach. One problem with RBH is that it will incorrectly predict a paralog as an ortholog when incomplete genome sequences or gene loss is involved. In addition, there is an increasing interest in identifying orthologs most likely to have retained similar function. 相似文献588.
Gwinn W Zhang M Mon S Sampey D Zukauskas D Kassebaum C Zmuda JF Tsai A Laird MW 《Protein expression and purification》2006,45(1):30-36
The anthrax toxin consists of three proteins, protective antigen (PA), lethal factor, and edema factor that are produced by the Gram-positive bacterium, Bacillus anthracis. Current vaccines against anthrax use PA as their primary component. In this study, we developed a scalable process to produce and purify multi-gram quantities of highly pure, recombinant PA (rPA) from Escherichia coli. The rPA protein was produced in a 50-L fermentor and purified to >99% purity using anion-exchange, hydrophobic interaction, and hydroxyapatite chromatography. The final yield of purified rPA from medium cell density fermentations resulted in approximately 2.7 g of rPA per kg of cell paste (approximately 270 mg/L) of highly pure, biologically active rPA protein. The results presented here exhibit the ability to generate multi-gram quantities of rPA from E. coli that may be used for the development of new anthrax vaccines and anthrax therapeutics. 相似文献
589.
Michael H Cho George R Washko Thomas J Hoffmann Gerard J Criner Eric A Hoffman Fernando J Martinez Nan Laird John J Reilly Edwin K Silverman 《Respiratory research》2010,11(1):30
Background
Numerous studies have demonstrated associations between genetic markers and COPD, but results have been inconsistent. One reason may be heterogeneity in disease definition. Unsupervised learning approaches may assist in understanding disease heterogeneity.Methods
We selected 31 phenotypic variables and 12 SNPs from five candidate genes in 308 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study cohort. We used factor analysis to select a subset of phenotypic variables, and then used cluster analysis to identify subtypes of severe emphysema. We examined the phenotypic and genotypic characteristics of each cluster.Results
We identified six factors accounting for 75% of the shared variability among our initial phenotypic variables. We selected four phenotypic variables from these factors for cluster analysis: 1) post-bronchodilator FEV1 percent predicted, 2) percent bronchodilator responsiveness, and quantitative CT measurements of 3) apical emphysema and 4) airway wall thickness. K-means cluster analysis revealed four clusters, though separation between clusters was modest: 1) emphysema predominant, 2) bronchodilator responsive, with higher FEV1; 3) discordant, with a lower FEV1 despite less severe emphysema and lower airway wall thickness, and 4) airway predominant. Of the genotypes examined, membership in cluster 1 (emphysema-predominant) was associated with TGFB1 SNP rs1800470.Conclusions
Cluster analysis may identify meaningful disease subtypes and/or groups of related phenotypic variables even in a highly selected group of severe emphysema subjects, and may be useful for genetic association studies. 相似文献590.
Jorg Brunner Floyd RA Wittink Martijs J Jonker Mark de Jong Timo M Breit Marja L Laine Johannes J de Soet Wim Crielaard 《BMC microbiology》2010,10(1):252