全文获取类型
收费全文 | 367篇 |
免费 | 103篇 |
出版年
2021年 | 6篇 |
2020年 | 2篇 |
2019年 | 2篇 |
2018年 | 9篇 |
2017年 | 6篇 |
2016年 | 7篇 |
2015年 | 14篇 |
2014年 | 15篇 |
2013年 | 22篇 |
2012年 | 25篇 |
2011年 | 24篇 |
2010年 | 16篇 |
2009年 | 20篇 |
2008年 | 17篇 |
2007年 | 24篇 |
2006年 | 29篇 |
2005年 | 22篇 |
2004年 | 16篇 |
2003年 | 13篇 |
2002年 | 13篇 |
2001年 | 11篇 |
2000年 | 11篇 |
1999年 | 9篇 |
1998年 | 7篇 |
1997年 | 6篇 |
1996年 | 5篇 |
1995年 | 8篇 |
1994年 | 5篇 |
1993年 | 13篇 |
1992年 | 11篇 |
1991年 | 7篇 |
1990年 | 15篇 |
1989年 | 7篇 |
1988年 | 4篇 |
1987年 | 5篇 |
1986年 | 4篇 |
1985年 | 5篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1978年 | 1篇 |
1977年 | 3篇 |
1976年 | 5篇 |
1975年 | 1篇 |
1974年 | 4篇 |
1973年 | 3篇 |
1972年 | 1篇 |
1970年 | 3篇 |
1969年 | 1篇 |
排序方式: 共有470条查询结果,搜索用时 15 毫秒
121.
Stuger R Woldringh CL van der Weijden CC Vischer NO Bakker BM van Spanning RJ Snoep JL Westerhoff HV 《Molecular biology reports》2002,29(1-2):79-82
The genes of E. coli are located on a circular chromosome of 4.6 million basepairs. This 1.6 mm long molecule is compressed into a nucleoid to fit inside the 1-2 m cell in a functional format. To examine the role of DNA supercoiling as nucleoid compaction force we modulated the activity of DNA gyrase by electronic, genetic, and chemical means. A model based on physical properties of DNA and other cell components predicts that relaxation of supercoiling expands the nucleoid. Nucleoid size did not increase after reduction of DNA gyrase activity by genetic or chemical means, but nucleoids did expand upon chemical inhibition of gyrase in chloramphenicol-treated cells, indicating that supercoiling may help to compress the genome. 相似文献
122.
123.
We investigated the effect of short-term exposure to cadmium and 2,4-dichlorophenoxy acetic acid on the digestive physiology
of Daphnia magna and the consequences for the bioenergetics of the organism. In both cases, ingestion was more drastically
reduced compared to digestive enzyme activity. Furthermore a differential shift in catabolism was noted: in general polysaccharidases
were less affected than the enzymes responsible for protein and lipid digestion. Comparison of the ‘1 h in vivo fluorescence’
criterion (Janssen & Persoone, 1993) with the ingestion and digestive enzyme activity revealed that this rapid screening assay
should be considered as a quantification of ingestion inhibition rather than a methodology assessing digestive enzyme inhibition.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
124.
We used the white gene as an enhancer trap and reporter of chromatin structure. We collected white+ transgene insertions presenting a peculiar pigmentation pattern in the eye: white expression is restricted to the dorsal half of the eye, with a clear-cut dorsal/ventral (D/V) border. This D/V pattern is stable and heritable, indicating that phenotypic expression of the white reporter reflects positional information in the developing eye. Localization of these transgenes led us to identify a unique genomic region encompassing 140 kb in 69D1-3 subject to this D/V effect. This region contains at least three closely related homeobox-containing genes that are constituents of the iroquois complex (IRO-C). IRO-C genes are coordinately regulated and implicated in similar developmental processes. Expression of these genes in the eye is regulated by the products of the Polycomb-group (Pc-G) and trithorax-group (trx-G) genes but is not modified by classical modifiers of position-effect variegation. Our results, together with the report of a Pc-G binding site in 69D, suggest that we have identified a novel cluster of target genes for the Pc-G and trx-G products. We thus propose that ventral silencing of the whole IRO-C in the eye occurs at the level of chromatin structure in a manner similar to that of the homeotic gene complexes, perhaps by local compaction of the region into a heterochromatin-like structure involving the Pc-G products. 相似文献
125.
Marcel Thalen Marian Venema Jan van den IJssel Luc Berwald Coen Beuvery Dirk Martens Johannes Tramper 《Biologicals》2006,34(3):213-220
Whooping cough vaccines are produced using different ranges of cultivation conditions and medium compositions, which are known to influence growth rate, virulence factor production and degradation, as well as the virulence factors' association to the cell. This study quantifies the impact of individual parameters on Pertussis Toxin (PT) production, using an optimized chemically defined medium as starting point, rather than a complex medium. A number of chemicals that are identified affect both growth rate and virulence factor production, which occur at similar levels in various commonly used production media. Also, degradation by proteolytic activity is shown to be an important parameter to monitor, since it significantly affects the PT yield. Low sodium concentrations, i.e. 50-75 mM rather than the conventional 100-140 mM, significantly increase the growth rate of the organism, the final optical density, as well as the association of PT to the cells. The absolute amount of biomass produced measured as dry weight, is similar for all sodium concentrations tested, contrary to earlier work. While it is known that high iron concentrations inhibit virulence factor production, it is shown here that iron-limited growth results in very high specific PT production. This finding may be used to produce a whole-cell vaccine with little biomass per dose, reducing whole-cell vaccine toxicity. The Bordetella pertussis strain 509 used here produces 30% more PT at 34 than at 37 degrees C, a commonly used cultivation temperature. The data in this study show that existing production processes for cellular and acellular vaccines can in principle be optimised considerably by taking simple measures. 相似文献
126.
127.
128.
129.
Mutations in the herpes simplex virus DNA polymerase gene can confer resistance to 9-beta-D-arabinofuranosyladenine. 总被引:23,自引:8,他引:15 下载免费PDF全文
Mutants of herpes simplex virus type 1 resistant to the antiviral drug 9-beta-D-arabinofuranosyladenine (araA) have been isolated and characterized. AraA-resistant mutants can be isolated readily and appear at an appreciable frequency in low-passage stocks of wild-type virus. Of 13 newly isolated mutants, at least 11 were also resistant to phosphonoacetic acid (PAA). Of four previously described PAA-resistant mutants, two exhibited substantial araA resistance. The araA resistance phenotype of one of these mutants, PAAr5, has been mapped to the HpaI-B fragment of herpes simplex virus DNA by marker transfer, and araA resistance behaved in marker transfer experiments as if it were closely linked to PAA resistance, a recognized marker for the viral DNA polymerase locus. PAAr5 induced viral DNA polymerase activity which was much less susceptible to inhibition by the triphosphate derivative of araA than was wild-type DNA polymerase. These genetic and biochemical data indicate that the herpes simplex virus DNA polymerase gene is a locus which, when mutated, can confer resistance to araA and thus that the herpes simplex virus DNA polymerase is a target for this antiviral drug. 相似文献
130.
Robbert J. van der Pijl Andrea A. Domenighetti Farah Sheikh Elisabeth Ehler Coen A. C. Ottenheijm Stephan Lange 《Biophysical reviews》2021,13(5):653
Muscle specific signaling has been shown to originate from myofilaments and their associated cellular structures, including the sarcomeres, costameres or the cardiac intercalated disc. Two signaling hubs that play important biomechanical roles for cardiac and/or skeletal muscle physiology are the N2B and N2A regions in the giant protein titin. Prominent proteins associated with these regions in titin are chaperones Hsp90 and αB-crystallin, members of the four-and-a-half LIM (FHL) and muscle ankyrin repeat protein (Ankrd) families, as well as thin filament-associated proteins, such as myopalladin. This review highlights biological roles and properties of the titin N2B and N2A regions in health and disease. Special emphasis is placed on functions of Ankrd and FHL proteins as mechanosensors that modulate muscle-specific signaling and muscle growth. This region of the sarcomere also emerged as a hotspot for the modulation of passive muscle mechanics through altered titin phosphorylation and splicing, as well as tethering mechanisms that link titin to the thin filament system. 相似文献