全文获取类型
收费全文 | 166篇 |
免费 | 14篇 |
出版年
2023年 | 1篇 |
2021年 | 2篇 |
2020年 | 1篇 |
2019年 | 4篇 |
2018年 | 1篇 |
2016年 | 1篇 |
2015年 | 4篇 |
2014年 | 5篇 |
2013年 | 10篇 |
2012年 | 10篇 |
2011年 | 13篇 |
2010年 | 9篇 |
2009年 | 4篇 |
2008年 | 6篇 |
2007年 | 6篇 |
2006年 | 8篇 |
2005年 | 4篇 |
2004年 | 12篇 |
2003年 | 7篇 |
2002年 | 10篇 |
2001年 | 2篇 |
2000年 | 5篇 |
1999年 | 3篇 |
1998年 | 1篇 |
1997年 | 6篇 |
1996年 | 1篇 |
1995年 | 5篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1992年 | 4篇 |
1991年 | 3篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1979年 | 1篇 |
1975年 | 2篇 |
1974年 | 5篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1969年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有180条查询结果,搜索用时 15 毫秒
1.
The paired lungs of the newt, Taricha granulosa, are simple, unbranched sacs, 3.5-5.0 cm in length. The inner epithelium overlying the pulmonary vein is differentiated into a mucociliary tract that extends the entire length of the lung. Populations of single, demembranated ciliary axonemes, 12-13 micron in length, can be isolated by extracting whole lungs or primary cultures of the ciliated epithelium with Triton X-100. The motile capabilities of the isolated axonemes are the highest yet obtained for any ciliary model. When exposed to a suitable reactivating medium containing Mg2+ and ATP, nearly 100% of the axonemes become motile. Uniform reactivation of high quality requires short extraction times, minimization of mechanical damage, and strict adherence to optimal conditions throughout the extraction, storage, and reactivation procedures. Significant deviations from either pH 7.0 or 0.12 M salt can lead to a rapid, irreversible decrease in the beat frequency of reactivated axonemes. Both DTT and EDTA serve to stabilize their motility. The isolated axonemes beat at 29.5 Hz in the presence of 1.75 mM ATP at 21 degrees C, matching the beat frequencies measured for cultured cells at the same temperature. With 5 mM ATP, beat frequencies over 40 Hz are measured. Our results show that neither the plasma membrane, accessory structures, nor hydrodynamic coupling of cilia are required for this activity and imply that the lack of these factors is not responsible for the low motile capabilities of ciliary models isolated previously. 相似文献
2.
Wesley Hicks Robert Ward David Edelstein Leon Hall Anthony Albino Robert Hard Bonnie Asch 《Cell biology international》1995,19(4):301-306
The cytokertatins in respiratory epithelial cells (REC) of human nasal polyps and turbinates were analyzed by immunohistochemistry. Cytokeratin 19 (CK19) was present in all REC, CK5 and 14 were expressed primarily in basal cells, and CK7, 8, and 18 were found in suprabasal cells. Differences in cytoplasmic locations were also apparent among the individual cytokeratins. CK13 was not detected in any REC of these tissues. The results indicate the profile of cytokeratins in REC of human nasal polyps and turbinates is essentially identical to that of REC in the more distal respiratory tract. 相似文献
3.
Wolf-Dietrich Hard Jens M. Warnecke Roland K. Hartmann 《Molecular biology reports》1995,22(2-3):161-169
Modification interference is a powerful method to identify important functional groups in RNA molecules. We review here recent developments of techniques to screen for chemical modifications that interfere with (i) binding of(pre-)tRNA to bacterial RNase P RNA or (ii) pre-tRNA cleavage by this ribozyme. For example, two studies have analyzed positions at which a substitution of sulfur for thepro-Rp oxygen affects tRNA binding [1] or catalysis [2]. The results emphasize the functional key role of a central core element present in all known RNase P RNA subunits. The four sulfur substitutions identified in one study [2] to inhibit the catalytic step also interfered with binding of tRNA toE. coli RNase P RNA [1]. This suggests that losses in binding energy due to the modification at these positions affect the enzyme-substrate and the enzyme-transition state complex. In addition, the two studies have revealed, for the first time, sites of direct metal ion coordination in RNase P RNA. The potentials, limitations and interpretational ambiguities of modification interference experiments as well as factors influencing their outcome are discussed.Abbreviations nt
nucleotide(s)
- PAGE
polyacrylamide gel electrophoresis 相似文献
4.
5.
Charles D. Waters Jeffrey J. Hard David E. Fast Curtis M. Knudsen William J. Bosch Kerry A. Naish 《Molecular ecology》2020,29(4):658-672
Genomic approaches permit direct estimation of inbreeding and its effect on fitness. We used genomic‐based estimates of inbreeding to investigate their relationship with eight adult traits in a captive‐reared Pacific salmonid that is released into the wild. Estimates were also used to determine whether alternative broodstock management approaches reduced risks of inbreeding. Specifically, 1,100 unlinked restriction‐site associated (RAD) loci were used to compare pairwise relatedness, derived from a relationship matrix, and individual inbreeding, estimated by comparing observed and expected homozygosity, across four generations in two hatchery lines of Chinook salmon that were derived from the same source. The lines are managed as “integrated” with the founding wild stock, with ongoing gene flow, and as “segregated” with no gene flow. While relatedness and inbreeding increased in the first generation of both lines, possibly due to population subdivision caused by hatchery initiation, the integrated line had significantly lower levels in some subsequent generations (relatedness: F2–F4; inbreeding F2). Generally, inbreeding was similar between the lines despite large differences in effective numbers of breeders. Inbreeding did not affect fecundity, reproductive effort, return timing, fork length, weight, condition factor, and daily growth coefficient. However, it delayed spawn timing by 1.75 days per one standard deviation increase in F (~0.16). The results indicate that integrated management may reduce inbreeding but also suggest that it is relatively low in a small, segregated hatchery population that maximized number of breeders. Our findings demonstrate the utility of genomics to monitor inbreeding under alternative management strategies in captive breeding programs. 相似文献
6.
Boas Felmy Pascal Songhet Emma Marie Caroline Slack Andreas J. Müller Marcus Kremer Laurye Van Maele Delphine Cayet Mathias Heikenwalder Jean-Claude Sirard Wolf-Dietrich Hardt 《PloS one》2013,8(10)
Infections, microbe sampling and occasional leakage of commensal microbiota and their products across the intestinal epithelial cell layer represent a permanent challenge to the intestinal immune system. The production of reactive oxygen species by NADPH oxidase is thought to be a key element of defense. Patients suffering from chronic granulomatous disease are deficient in one of the subunits of NADPH oxidase. They display a high incidence of Crohn’s disease-like intestinal inflammation and are hyper-susceptible to infection with fungi and bacteria, including a 10-fold increased risk of Salmonellosis. It is not completely understood which steps of the infection process are affected by the NADPH oxidase deficiency. We employed a mouse model for Salmonella diarrhea to study how NADPH oxidase deficiency (Cybb
−/−) affects microbe handling by the large intestinal mucosa. In this animal model, wild type S. Typhimurium causes pronounced enteropathy in wild type mice. In contrast, an avirulent S. Typhimurium mutant (S.Tmavir; invGsseD), which lacks virulence factors boosting trans-epithelial penetration and growth in the lamina propria, cannot cause enteropathy in wild type mice. We found that Cybb
−/− mice are efficiently infected by S.Tmavir and develop enteropathy by day 4 post infection. Cell depletion experiments and infections in Cybb
−/−
Myd88
−/− mice indicated that the S.Tmavir-inflicted disease in Cybb
−/− mice hinges on CD11c+CX3CR1+ monocytic phagocytes mediating colonization of the cecal lamina propria and on Myd88-dependent proinflammatory immune responses. Interestingly, in mixed bone marrow chimeras a partial reconstitution of Cybb-proficiency in the bone marrow derived compartment was sufficient to ameliorate disease severity. Our data indicate that NADPH oxidase expression is of key importance for restricting the growth of S.Tmavir in the mucosal lamina propria. This provides important insights into microbe handling by the large intestinal mucosa and the role of NADPH oxidase in maintaining microbe-host mutualism at this exposed body surface. 相似文献
7.
The C-type lectin RegIIIβ can kill certain Gram-positive and Gram-negative bacteria. The susceptibility of S. Typhimurium depends on the bacterial growth phase, i.e., bacteria from the logarithmic growth phase do bind RegIIIβ and are subsequently killed. Lipid A is one of the bacterial targets for RegIIIβ. However, at the molecular level, it is not understood how RegIIIβ interacts with and kills Gram-negative bacteria. Here, we show that RegIIIβ interacts with Gram-negative bacteria in two distinct steps. Initially, it binds to surface-exposed lipid A. The lipid A can be shielded by the O-antigen of lipopolysaccharide (LPS), as indicated by the exquisite susceptibility of wbaP mutants to RegIIIβ-mediated killing. Increased cell viability after incubation with an anti-lipid A antibody also supports this conclusion. This RegIIIβ-binding permeabilizes the outer membrane to hydrophobic dyes like Ethidium bromide or to bulky bacteriolytic enzymes like lysozyme. Conversely, compromising the outer membrane integrity by the mild detergent Triton X-100 enhances the antibacterial effect of RegIIIβ. Based on our observations, we conclude that RegIIIβ interacts with Gram-negative bacteria in two subsequent steps. Initially, it binds to the outer membrane thus leading to outer membrane permeabilization. This initial step is necessary for RegIIIβ to reach a second, still not well understood target site (presumably localized in the periplasm or the cytoplasmic membrane), thereby triggering bacterial death. This provides novel insights into the outer membrane-step of the bactericidal mechanism of RegIIIβ. 相似文献
8.
Wolf-Dietrich Gürtler 《Der Zoologische Garten (in deutscher Sprache / in German)》2013,82(3-4):167-189
In the Zoom Erlebniswelt Gelsenkirchen the third and last biogeographical area dedicated to the Asian fauna was opened in March 2010 covering a total area of five hectares. In May 2013 a new enclosure for tigers was added. The emphasis of the Asia area lies on a 4700 m2 tropical hall with mammals and birds, and Asian gastronomic facilities as well. Included is a mixed species exhibit for orangutans (Pongo abelii), northern plains grey langurs (Semnopithecus entellus) and Asian small clawed otters (Aonyx cinerea). Along a 1.3 km outside path enclosures for some species of colder climates were built, too. The transformation of the former Ruhr Zoo Gelsenkirchen to the modern ZOOM Erlebniswelt herewith is brought to a close. 相似文献
9.
The DNA damage checkpoint pathways exert multiple controls on the efficiency and outcome of the repair of a double-stranded DNA gap 总被引:2,自引:0,他引:2 下载免费PDF全文
A DNA gap repair assay was used to determine the effect of mutations in the DNA damage checkpoint system on the efficiency and outcome (crossover/non-crossover) of recombinational DNA repair. In Saccharomyces cerevisiae gap repair is largely achieved by homologous recombination. As a result the plasmid either integrates into the chromosome (indicative of a crossover outcome) or remains extrachromosomal (indicative of a non-crossover outcome). Deletion mutants of the MEC1 and RAD53 checkpoint kinase genes exhibited a 5-fold decrease in gap repair efficiency, showing that 80% of the gap repair events depended on functional DNA damage checkpoints. Epistasis analysis suggests that the DNA damage checkpoints affect gap repair by modulating Rad51 protein-mediated homologous recombination. While in wild-type cells only ~25% of the gap repair events were associated with a crossover outcome, Mec1-deficient cells exhibited a >80% crossover association. Also mutations in the effector kinases Rad53, Chk1 and Dun1 were found to affect crossover association of DNA gap repair to various degrees. The data suggest that the DNA damage checkpoints are important for the optimal functioning of recombinational DNA repair with multiple terminal targets to modulate the efficiency and outcome of homologous recombination. 相似文献
10.
Buchwald G Friebel A Galán JE Hardt WD Wittinghofer A Scheffzek K 《The EMBO journal》2002,21(13):3286-3295
The bacterial enteropathogen Salmonella typhimurium employs a type III secretion system to inject bacterial toxins into the host cell cytosol. These toxins transiently activate Rho family GTP-binding protein-dependent signaling cascades to induce cytoskeletal rearrangements. One of these translocated Salmonella toxins, SopE, can activate Cdc42 in a Dbl-like fashion despite its lack of sequence similarity to Dbl-like proteins, the Rho-specific eukaryotic guanine nucleotide exchange factors. To elucidate the mechanism of SopE-mediated guanine nucleotide exchange, we have analyzed the structure of the complex between a catalytic fragment of SopE and Cdc42. SopE binds to and locks the switch I and switch II regions of Cdc42 in a conformation that promotes guanine nucleotide release. This conformation is strikingly similar to that of Rac1 in complex with the eukaryotic Dbl-like exchange factor Tiam1. However, the catalytic domain of SopE has an entirely different architecture from that of Tiam1 and interacts with the switch regions via different amino acids. Therefore, SopE represents the first example of a non-Dbl-like protein capable of inducing guanine nucleotide exchange in Rho family proteins. 相似文献