全文获取类型
收费全文 | 469篇 |
免费 | 47篇 |
出版年
2019年 | 3篇 |
2018年 | 6篇 |
2017年 | 7篇 |
2016年 | 3篇 |
2015年 | 15篇 |
2014年 | 14篇 |
2013年 | 20篇 |
2012年 | 24篇 |
2011年 | 20篇 |
2010年 | 27篇 |
2009年 | 9篇 |
2008年 | 31篇 |
2007年 | 22篇 |
2006年 | 20篇 |
2005年 | 21篇 |
2004年 | 9篇 |
2003年 | 10篇 |
2002年 | 5篇 |
2001年 | 12篇 |
2000年 | 27篇 |
1999年 | 14篇 |
1998年 | 9篇 |
1997年 | 5篇 |
1995年 | 4篇 |
1994年 | 7篇 |
1992年 | 11篇 |
1991年 | 12篇 |
1990年 | 10篇 |
1989年 | 17篇 |
1988年 | 11篇 |
1987年 | 14篇 |
1986年 | 14篇 |
1985年 | 8篇 |
1984年 | 6篇 |
1982年 | 4篇 |
1981年 | 3篇 |
1979年 | 3篇 |
1977年 | 3篇 |
1975年 | 4篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1971年 | 2篇 |
1970年 | 2篇 |
1969年 | 3篇 |
1967年 | 2篇 |
1955年 | 4篇 |
1948年 | 2篇 |
1942年 | 2篇 |
1903年 | 2篇 |
1899年 | 2篇 |
排序方式: 共有516条查询结果,搜索用时 15 毫秒
71.
I.R. McDonald M. Upton G. Hall R.W. Pickup C. Edwards J.R. Saunders D.A. Ritchie J.C. Murrell 《Microbial ecology》1999,38(3):225-233
Abstract
Methane production and methane oxidation potential were measured in a 30 cm peat core from the Moorhouse Nature Reserve, UK.
The distribution of known groups of methanogens and methane oxidizing bacteria throughout this peat core was assessed. Using
16S rRNA gene retrieval and functional gene probing with genes encoding key proteins in methane oxidation and methanogenesis,
several major groups of microorganisms were detected. Methane production and oxidation was detected in all depths of the peat
core. PCR amplification and oligonucleotide probing experiments using DNA isolated from all sections of the peat core detected
methanotrophs from the groups Methylosinus and Methylococcus and methanogens from the groups Methanosarcinaceae, Methanococcaceae, and Methanobacteriaceae. 16S rDNA sequences amplified with the Methylosinus-specific primer were shown to have a high degree of identity with 16S rDNA sequences previously detected in acidic environments.
However, no methanogen sequences were detected by the probes available in this study in the sections of the peat core (above
7 cm) where the majority of methanogenesis occurred, either because of low methanogen numbers or because of the presence of
novel methanogen sequences.
Received: 9 March 1999; Accepted: 21 June 1999 相似文献
72.
Kristen Upton Matthew Meyers Ann-Gerd Thorsell Tobias Karlberg Jacob Holechek Robert Lease Garrett Schey Emily Wolf Adrianna Lucente Herwig Schüler Dana Ferraris 《Bioorganic & medicinal chemistry letters》2017,27(13):2907-2911
A series of (Z)-4-(3-carbamoylphenylamino)-4-oxobut-2-enyl amides were synthesized and tested for their ability to inhibit the mono-(ADP-ribosyl)transferase, PARP14 (a.k.a. BAL-2; ARTD-8). Two synthetic routes were established for this series and several compounds were identified as sub-micromolar inhibitors of PARP14, the most potent of which was compound 4t, IC50 = 160 nM. Furthermore, profiling other members of this series identified compounds with >20-fold selectivity over PARP5a/TNKS1, and modest selectivity over PARP10, a closely related mono-(ADP-ribosyl)transferase. 相似文献
73.
Inspiratory muscle weakness in patients with COPD is of major clinical relevance. For instance, maximum inspiratory pressure generation is an independent determinant of survival in severe COPD. Traditionally, inspiratory muscle weakness has been ascribed to hyperinflation-induced diaphragm shortening. However, more recently, invasive evaluation of diaphragm contractile function, structure, and biochemistry demonstrated that cellular and molecular alterations occur, of which several can be considered pathologic of nature. Whereas the fiber type shift towards oxidative type I fibers in COPD diaphragm is regarded beneficial, rendering the overloaded diaphragm more resistant to fatigue, the reduction of diaphragm fiber force generation in vitro likely contributes to diaphragm weakness. The reduced diaphragm force generation at single fiber level is associated with loss of myosin content in these fibers. Moreover, the diaphragm in COPD is exposed to oxidative stress and sarcomeric injury. This review postulates that the oxidative stress and sarcomeric injury activate proteolytic machinery, leading to contractile protein wasting and, consequently, loss of force generating capacity of diaphragm fibers in patients with COPD. Interestingly, several of these presumed pathologic alterations are already present early in the course of the disease (GOLD I/II), although these patients appear not limited in their daily life activities. Treatment of diaphragm dysfunction in COPD is complex since its etiology is unclear, but recent findings indicate the ubiquitin-proteasome pathway as a prime target to attenuate diaphragm wasting in COPD. 相似文献
74.
75.
Duplication and transmission of chromosomes require precise control of chromosome replication and segregation. Here we present evidence that RecG is a major factor influencing these processes in bacteria. We show that the extensive DnaA-independent stable DNA replication observed without RecG can lead to replication of any area of the chromosome. This replication is further elevated following irradiation with UV light and appears to be perpetuated by secondary events that continue long after the elimination of UV lesions. The resulting pathological cascade is associated with an increased number of replication forks traversing the chromosome, sometimes with extensive regional amplification of the chromosome, and with the accumulation of highly branched DNA intermediates containing few Holliday junctions. We propose that the cascade is triggered by replication fork collisions that generate 3' single-strand DNA flaps, providing sites for PriA to initiate re-replication of the DNA and thus to generate linear duplexes that provoke recombination, allowing priming of even further replication. Our results shed light on why termination of replication in bacteria is normally limited to a single encounter of two forks and carefully orchestrated within a restricted area, and explain how a system of multiple forks and random termination can operate in eukaryotes. 相似文献
76.
77.
Paul D. Upton Rachel J. Davies Richard C. Trembath Nicholas W. Morrell 《The Journal of biological chemistry》2009,284(23):15794-15804
78.
79.
A comparison of testing methods for constituents of Ginkgo biloba was performed as part of the process for determining which of the many available analytical methods was most appropriate for inclusion in the American Herbal Pharmacopoeia (AHP). Three primary methods were reviewed: those adopted by the European Pharmacopoeia, the National Science Foundation-Institute for Nutraceutical Advancement (NSF-INA) and the United States Pharmacopeia. Methods were compared by evaluating sample preparation and hydrolysis, precision and methods of total flavonol glycoside calculation by two independent laboratories. The AHP adopted the method of NSF-INA for inclusion in the AHP monograph owing to observed superiority of this method in terms of precision, glycoside calculation, ease of sample preparation and chromatographic parameters. 相似文献
80.
Evidence for CDK-dependent and CDK-independent functions of the murine gammaherpesvirus 68 v-cyclin
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Gamma-2 herpesviruses encode homologues of mammalian D-type cyclins (v-cyclins), which likely function to manipulate the cell cycle, thereby providing a cellular environment conducive to virus replication and/or reactivation from latency. We have previously shown that the v-cyclin of murine gammaherpesvirus 68 is an oncogene that binds and activates cellular cyclin-dependent kinases (CDKs) and is required for efficient reactivation from latency. To determine the contribution of v-cyclin-mediated cell cycle regulation to the viral life cycle, recombinant viruses in which specific point mutations (E133V or K104E) were introduced into the v-cyclin open reading frame were generated, resulting in the disruption of CDK binding and activation. While in vitro growth of these mutant viruses was unaffected, lytic replication in the lungs following low-dose intranasal inoculation was attenuated for both mutants deficient in CDK binding as well as virus in which the entire v-cyclin open reading frame was disrupted by the insertion of a translation termination codon. This replication defect was not apparent in spleens of mice following intraperitoneal inoculation, suggesting a cell type- and/or route-specific dependence on v-cyclin-CDK interactions during the acute phase of virus infection. Notably, although a v-cyclin-null virus was highly attenuated for reactivation from latency, the E133V v-cyclin CDK-binding mutant exhibited only a modest defect in virus reactivation from splenocytes, and neither the E133V nor K104E v-cyclin mutants were compromised in reactivation from peritoneal exudate cells. Taken together, these data suggest that lytic replication and reactivation in vivo are differentially regulated by CDK-dependent and CDK-independent functions of v-cyclin, respectively. 相似文献