全文获取类型
收费全文 | 660篇 |
免费 | 40篇 |
专业分类
700篇 |
出版年
2022年 | 3篇 |
2021年 | 9篇 |
2020年 | 4篇 |
2019年 | 7篇 |
2018年 | 7篇 |
2017年 | 2篇 |
2016年 | 9篇 |
2015年 | 14篇 |
2014年 | 23篇 |
2013年 | 35篇 |
2012年 | 17篇 |
2011年 | 28篇 |
2010年 | 29篇 |
2009年 | 19篇 |
2008年 | 29篇 |
2007年 | 37篇 |
2006年 | 36篇 |
2005年 | 29篇 |
2004年 | 38篇 |
2003年 | 42篇 |
2002年 | 32篇 |
2001年 | 18篇 |
2000年 | 20篇 |
1999年 | 10篇 |
1998年 | 14篇 |
1997年 | 20篇 |
1996年 | 9篇 |
1995年 | 7篇 |
1994年 | 6篇 |
1993年 | 3篇 |
1992年 | 7篇 |
1991年 | 9篇 |
1990年 | 13篇 |
1989年 | 14篇 |
1988年 | 9篇 |
1987年 | 4篇 |
1986年 | 11篇 |
1985年 | 10篇 |
1984年 | 5篇 |
1983年 | 8篇 |
1982年 | 6篇 |
1981年 | 9篇 |
1980年 | 8篇 |
1979年 | 7篇 |
1978年 | 2篇 |
1977年 | 5篇 |
1975年 | 3篇 |
1974年 | 3篇 |
1973年 | 4篇 |
1968年 | 2篇 |
排序方式: 共有700条查询结果,搜索用时 15 毫秒
11.
12.
13.
Y Iwasa 《Journal of theoretical biology》1978,72(4):611-626
Using Pontryagin's maximum principle, the optimal death strategy that maximizes the total reproduction of a population, which has the density dependent growth rate and the weight dependent reproduction, is investigated. As the result, it is shown that the optimal survival curve has a critical age, before which the mortality takes the highest admissible value and after which the lowest. In a population with this optimal death strategy, the change of resource level affects the length of the stage of high mortality. The switching age is explicitly calculated in a special case with a simple growth rate function and a simple weight dependence of reproduction. The average value of mortality or growth coefficient through the prereproductive stages are calculated and compared with the Le Cren's data, where trout was reared in varying resource levels. 相似文献
14.
Kenichiro Kinouchi Atsuhiro Ichihara Motoaki Sano Ge-Hong Sun-Wada Yoh Wada Hiroki Ochi Toru Fukuda Kanako Bokuda Hideaki Kurosawa Naohiro Yoshida Shu Takeda Keiichi Fukuda Hiroshi Itoh 《PloS one》2013,8(11)
The ATPase 6 accessory protein 2 (ATP6AP2)/(pro)renin receptor (PRR) is essential for the biogenesis of active vacuolar H+-ATPase (V-ATPase). Genetic deletion of ATP6AP2/PRR causes V-ATPase dysfunction and compromises vesicular acidification. Here, we characterized the domains of ATP6AP2/PRR involved in active V-ATPase biogenesis. Three forms of ATP6AP2/PRR were found intracellularly: full-length protein and the N- and C-terminal fragments of furin cleavage products, with the N-terminal fragment secreted extracellularly. Genetic deletion of ATP6AP2/PRR did not affect the protein stability of V-ATPase subunits. The extracellular domain (ECD) and transmembrane domain (TM) of ATP6AP2/PRR were indispensable for the biogenesis of active V-ATPase. A deletion mutant of ATP6AP2/PRR, which lacks exon 4-encoded amino acids inside the ECD (Δ4M) and causes X-linked mental retardation Hedera type (MRXSH) and X-linked parkinsonism with spasticity (XPDS) in humans, was defective as a V-ATPase-associated protein. Prorenin had no effect on the biogenesis of active V-ATPase. The cleavage of ATP6AP2/PRR by furin seemed also dispensable for the biogenesis of active V-ATPase. We conclude that the N-terminal ECD of ATP6AP2/PRR, which is also involved in binding to prorenin or renin, is required for the biogenesis of active V-ATPase. The V-ATPase assembly occurs prior to its delivery to the trans-Golgi network and hence shedding of ATP6AP2/PRR would not affect the biogenesis of active V-ATPase. 相似文献
15.
Yoh Wada Ge‐Hong Sun‐Wada Nobuyuki Kawamura Jyunichiro Yasukawa 《Birth defects research. Part C, Embryo today : reviews》2016,108(1):33-44
Eukaryotes have evolved an array of membrane compartments constituting secretory and endocytic pathways that allow the flow of materials. Both pathways perform important regulatory roles. The secretory pathway is essential for the production of extracellular, secreted signal molecules, but its function is not restricted to a mere route connecting intra‐ and extracellular compartments. Post‐translational modifications also play an integral function in the secretory pathway and are implicated in developmental regulation. The endocytic pathway serves as a platform for relaying signals from the extracellular stimuli to intracellular mediators, and then ultimately inducing signal termination. Here, we discuss recent studies showing that dysfunction in membrane dynamics causes patterning defects in embryogenesis and tissue morphogenesis in mammals. Birth Defects Research (Part C) 108:33–44, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
16.
An experimental design and a statistical method for the estimation of the clustering-response activity of lymphocytosis-promoting factor (LPF) in Chinese hamster ovary cells growing in wells on a microplate were investigated. The scoring method introduced by Ipsen was adopted to express the grade of the clustering response rather than the end-point method generally used. The scoring method was validated by statistical analyses. The grade of response varied with the location of the wells on a microplate, and thus the expression of the clustering activity of a test sample in terms of the end-point may be inadequate in terms of accuracy and reproducibility. It was shown that the allocation of test samples to individual wells according to a Latin square design minimized the effect of the location of wells on the clustering response. Under such experimental conditions, a fairly precise and reproducible method for the quantification of the clustering activity was developed. 相似文献
17.
Miyakoshi A Yoon WK Jee Y Matsumoto Y 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(12):6371-6378
Like Lewis rats, DA rats are an experimental autoimmune encephalomyelitis (EAE)-susceptible strain and develop severe EAE upon immunization with myelin basic protein (MBP). However, there are several differences between the two strains. In the present study we induced acute EAE in DA rats by immunization with MBP and MBP peptides and examined the Ag specificity and TCR repertoire of encephalitogenic T cells. It was found that although immunization with MBP and a peptide corresponding to its 62-75 sequence (MBP(62-75)) induced clinical EAE, the responses of lymph node T cells isolated from MBP-immunized rats to MBP(62-75) was marginal, indicating that this peptide contains major encephalitogenic, but not immunodominant, epitopes. The TCR analysis by CDR3 spectratyping of spinal cord T cells revealed that Vbeta10 and Vbeta15 spectratype expansion was always found in MBP(62-75)-immunized symptomatic rats. On the basis of these findings, we examined the encephalitogenicity of Vbeta10- and Vbeta15-positive T cells. First, the adoptive transfer experiments revealed that Vbeta10-positive T line cells derived from MBP(62-75)-immunized rats induced clinical EAE in recipients. Second, administration of DNA vaccines encoding Vbeta10 and Vbeta15, alone or in combination, ameliorated MBP(62-75)-induced EAE. Collectively, it was strongly suggested that Vbeta10- and Vbeta15-positive T cells are encephalitogenic. Analyses of the Ag specificity and T cell repertoire of pathogenic T cells performed in this study provide useful information for designing specific immunotherapies against autoimmune diseases. 相似文献
18.
Induction of cytochrome P450 1A is required for circulation failure and edema by 2,3,7,8-tetrachlorodibenzo-p-dioxin in zebrafish 总被引:1,自引:0,他引:1
Teraoka H Dong W Tsujimoto Y Iwasa H Endoh D Ueno N Stegeman JJ Peterson RE Hiraga T 《Biochemical and biophysical research communications》2003,304(2):223-228
The mechanism of toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is thought to result from changes in gene expression via the aryl hydrocarbon receptor (AHR). The induction of cytochrome P450 1A (CYP1A) in various organs is a cardinal effect of TCDD. However, whether CYP1A is involved in endpoints of TCDD toxicity is controversial. We investigated the role of CYP1A in TCDD-induced developmental toxicities using gene knock-down with morpholino antisense oligos. Exposure of zebrafish embryos to TCDD, at concentrations eliciting the hallmark endpoints of developmental toxicity, induced CYP1A in the heart and vascular endothelium throughout the body. This induction by TCDD was markedly inhibited by morpholinos to zebrafish arylhydrocarbon receptor 2 (zfAHR2-MO) and to zebrafish CYP1A (zfCYP1A-MO). The zfAHR2-MO but not the zfCYP1A-MO inhibited zfCYP1A mRNA expression, indicating the specificities of these morpholinos. Injection of either zfAHR2-MO or zfCYP1A-MO blocked the representative signs of TCDD developmental toxicity in zebrafish, pericardial edema and trunk circulation failure. The morpholinos appeared do not affect normal development in TCDD-untreated embryos. These results suggest a mediatory role of zfCYP1A induction through zfAHR2 activation in causing circulation failure by TCDD in zebrafish. This is the first molecular evidence demonstrating an essential requirement for CYP1A induction in TCDD-evoked developmental toxicities in any vertebrate species. 相似文献
19.
Suzuki J Ohnishi H Wada A Hirayama T Ohno H Ueda N Yasuda H Iiri T Wada Y Futai M Mashima H 《The Journal of biological chemistry》2003,278(28):25585-25590
The Helicobacter pylori-produced cytotoxin VacA induces intracellular vacuolation. The formed vacuole is assumed to be a hybrid of late endosome and lysosome. To elucidate the molecular mechanism of VacA-induced vacuolation, we examined the participation of syntaxin 7 in the human gastric epithelial cell line AGS. Immunocytochemistry revealed that endogenous syntaxin 7 was localized to vacuoles induced by VacA. Northern and Western blotting demonstrated that VacA intoxication increased syntaxin 7 mRNA and protein expression, respectively, in a time-dependent manner. Transient transfection of dominant-negative mutant syntaxin 7, which lacks a carboxyl-terminal transmembrane domain, inhibited VacA-induced vacuolation. In contrast, transient transfection of wild-type syntaxin 7, dominant-negative mutant syntaxin 1a, or dominant-negative mutant syntaxin 4 did not alter VacA-induced vacuolation. Furthermore, under VacA treatment, neutral red dye uptake, a parameter of VacA-induced vacuolation, was inhibited in cells stably transfected with mutant syntaxin 7 but not in cells stably transfected with wild-type syntaxin 7, mutant syntaxin 1a, or mutant syntaxin 4. Sequential immunocytochemical observation confirmed that expression of mutant syntaxin 7 did not affect VacA attachment to or internalization into AGS cells. We suggest that syntaxin 7 is involved in the intracellular vacuolation induced by VacA. 相似文献
20.
Competition over mates takes many forms and has far-reaching consequences for many organisms. Recent work suggests that relative reproductive rates of males and females, sperm competition and quality variation among mates affect the strength of sexual selection. Song, other display, body size, visual ornaments and material resource offerings are often sexually selected. There is much empirical evidence of mate choice, and its evolution is clarified by mathematical models. Recent advances in theory also consider costs of choice, effects of deleterious mutations, fast and slow evolution of preferences and preferred traits, and simultaneous preferences for several traits. Contests over mates are important; so is sperm competition, scrambles, endurance rivalry, and coercion. The latter mechanisms have received less attention than mate choice. Sexual selection may explain puzzling aspects of plant pollination biology. 相似文献