全文获取类型
收费全文 | 755篇 |
免费 | 37篇 |
出版年
2023年 | 1篇 |
2022年 | 11篇 |
2021年 | 19篇 |
2020年 | 6篇 |
2019年 | 5篇 |
2018年 | 7篇 |
2017年 | 9篇 |
2016年 | 11篇 |
2015年 | 48篇 |
2014年 | 51篇 |
2013年 | 29篇 |
2012年 | 47篇 |
2011年 | 57篇 |
2010年 | 29篇 |
2009年 | 29篇 |
2008年 | 43篇 |
2007年 | 28篇 |
2006年 | 44篇 |
2005年 | 43篇 |
2004年 | 46篇 |
2003年 | 35篇 |
2002年 | 32篇 |
2001年 | 33篇 |
2000年 | 29篇 |
1999年 | 30篇 |
1998年 | 10篇 |
1997年 | 6篇 |
1996年 | 8篇 |
1995年 | 4篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1991年 | 4篇 |
1990年 | 6篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 2篇 |
1970年 | 2篇 |
排序方式: 共有792条查询结果,搜索用时 46 毫秒
81.
To investigate the requirement for pRb in myogenic differentiation, a floxed Rb allele was deleted either in proliferating myoblasts or after differentiation. Myf5-Cre mice, lacking pRb in myoblasts, died immediately at birth and exhibited high numbers of apoptotic nuclei and an almost complete absence of myofibers. In contrast, MCK-Cre mice, lacking pRb in differentiated fibers, were viable and exhibited a normal muscle phenotype and ability to regenerate. Induction of differentiation of Rb-deficient primary myoblasts resulted in high rates of apoptosis and a total inability to form multinucleated myotubes. Upon induction of differentiation, Rb-deficient myoblasts up-regulated myogenin, an immediate early marker of differentiation, but failed to down-regulate Pax7 and exhibited growth in low serum conditions. Primary myoblasts in which Rb was deleted after expression of differentiated MCK-Cre formed normal multinucleated myotubes that did not enter S-phase in response to serum stimulation. Therefore, Rb plays a crucial role in the switch from proliferation to differentiation rather than maintenance of the terminally differentiated state. 相似文献
82.
Münger K Baldwin A Edwards KM Hayakawa H Nguyen CL Owens M Grace M Huh K 《Journal of virology》2004,78(21):11451-11460
83.
Dae-Soo Kim Jae-Won Huh Young-Hyun Kim Sang-Je Park Kyu-Tae Chang 《Molecules and cells》2010,30(1):77-87
A dual coding event, which is the translation of different isoforms from a single gene, is one of the special patterns among
the alternative splicing events. This is an important mechanism for the regulation of protein diversity in human and mouse
genomes. Although the regulation for dual coding events has been characterized in a few genes, the individual mechanism remains
unclear. Numerous studies have described the exonization of transposable elements, which is the splicing mediated insertion
of transposable element sequence fragments into mature mRNAs. Therefore, in this study, we investigated the number of transposable
element (TE)-derived dual coding genes in human, chimpanzee and mouse genomes. TE fusion exons appeared in the dual coding
regions of 309 human genes. Functional protein domain alterations by TE-derived dual coding events were observed in 129 human
genes. Comparative TE-derived dual coding events were also analyzed in chimpanzee and mouse orthologs. Seventy chimpanzee
orthologs had TE-derived dual coding events, but mouse orthologs did not have any TE-derived dual coding events. Taken together,
our analyses listed the number of TE-derived dual coding genes which could be investigated by experimental analysis and suggested
that TE-derived dual coding events were major sources for the functional diversity of human genes, but not mouse genes. 相似文献
84.
85.
The nature of the association between ischemic stroke and Alzheimer’s disease (AD) at the cellular and molecular level is still unknown. We evaluated the effect of ischemic neuronal insults on the regulation of amyloid precursor protein (APP) processing. We used an in vitro model of cerebral ischemia (oxygen-glucose deprivation) to evaluate the effect of ischemic neuronal insults on the amyloidogenic and non-amyloidogenic pathways using human neuroblastoma cell line and primary cultured cells of transgenic mice which expressed human APP (Tg2576). Ischemic neuronal insults increased the production of Aβ in Tg2576 primary culture cells compared to controls. A disintegrin and metalloprotease 10 (ADAM 10) was markedly increased in early stage of ischemic insults, which was followed by decreased level of ADAM 10 expression in later stage. The protein and mRNA expression of β-site cleavage enzyme (BACE) and BACE activity was not significantly different between the group of ischemic insults and control. By contrast, the activity of γ-secretase was significantly increased after 4 h of ischemic insults, as compared to controls. The present study showed that the ischemic neuronal insults increased the production of Aβ by influencing APP metabolism, which may link the role of ischemic insults to the pathogenesis of AD. 相似文献
86.
Isolation of epithelial stem cells from dermis by a three-dimensional culture system 总被引:5,自引:0,他引:5
Medina RJ Kataoka K Takaishi M Miyazaki M Huh NH 《Journal of cellular biochemistry》2006,98(1):174-184
Skin is a representative self-renewing tissue containing stem cells. Although many attempts have been made to define and isolate skin-derived stem cells, establishment of a simple and reliable isolation procedure remains a goal to be achieved. Here, we report the isolation of cells having stem cell properties from mouse embryonic skin using a simple selection method based on an assumption that stem cells may grow in an anchorage-independent manner. We inoculated single cell suspensions prepared from mouse embryonic dermis into a temperature-sensitive gel and propagated the resulting colonies in a monolayer culture. The cells named dermis-derived epithelial progenitor-1 (DEEP) showed epithelial morphology and grew rapidly to a more than 200 population doubling level over a period of 250 days. When the cells were kept confluent, they spontaneously formed spheroids and continuously grew even in spheroids. Immunostaining revealed that all of the clones were positive for the expression of cytokeratin-8, -18, -19, and E-cadherin and negative for the expression of cytokeratin-1, -5, -6, -14, -20, vimentin, nestin, a ckit. Furthermore, they expressed epithelial stem cell markers such as p63, integrin beta1, and S100A6. On exposure to TGFbeta in culture, some of DEEP-1 cells expressed alpha-smooth muscle actin. When the cells were transplanted into various organs of adult SCID mice, a part of the inoculated cell population acquired neural, hepatic, and renal cell properties. These results indicate that the cells we isolated were of epithelial stem cell origin and that our new approach is useful for isolation of multipotent stem cells from skin tissues. 相似文献
87.
Huh YJ Kim JM Kim H Song H So H Lee SY Kwon SB Kim HJ Kim HH Lee SH Choi Y Chung SC Jeong DW Min BM 《Cell death and differentiation》2006,13(7):1138-1146
This study sought to characterize the reduced glutathione (GSH)/oxidized GSSG ratio during osteoclast differentiation and determine whether changes in the intracellular redox status regulate its differentiation through a RANKL-dependent signaling pathway. A progressive decrease of the GSH/GSSG ratio was observed during osteoclast differentiation, and the phenomenon was dependent on a decrease in total glutathione via downregulation of expression of the gamma-glutamylcysteinyl synthetase modifier gene. Glutathione depletion by L-buthionine-(S,R)-sulfoximine (BSO) was found to inhibit osteoclastogenesis by blocking nuclear import of NF-kappaB and AP-1 in RANKL-propagated signaling and bone pit formation by increasing BSO concentrations in mature osteoclasts. Furthermore, intraperitoneal injection of BSO in mice resulted in an increase in bone density and a decrease of the number of osteoclasts in bone. Conversely, glutathione repletion with either N-acetylcysteine or GSH enhanced osteoclastogenesis. These findings indicate that redox status decreases during osteoclast differentiation and that this modification directly regulates RANKL-induced osteoclastogenesis. 相似文献
88.
Recently, secretory granule Ca(2+) storage protein chromogranin B (CGB) was shown to be present in the nucleoplasm proper in a complex structure that consists of the inositol 1,4,5-trisphosphate receptor (IP(3)R)/Ca(2+) channels and the phospholipids. Further, the amounts of IP(3)Rs present in the nucleus of bovine chromaffin cells were shown to be comparable to that of the endoplasmic reticulum. Therefore, we investigated here the potential contribution of nuclear CGB on the IP(3)-dependent Ca(2+) mobilization in the nucleus, using both neuroendocrine PC12 and nonneuroendocrine NIH3T3 cells. Chromogranin A (CGA) expression in the NIH3T3 cells, which do not contain intrinsic chromogranins, increased the IP(3)-induced Ca(2+) releases in the nucleus by 45%, while CGB expression in the same cells increased the IP(3)-induced Ca(2+) releases in the nucleus by 80%. Microinjection of IP(3) into the nucleus of CGB-expressing NIH3T3 cells increased the IP(3)-dependent nuclear Ca(2+) mobilization approximately 3-fold, whereas in CGA-expressing cells it remained the same as that of control cells. In contrast, inhibition of CGA expression in PC12 cells by siRNA treatment decreased the IP(3)-induced Ca(2+) releases in the nucleus by 17%, while inhibition of CGB expression decreased the IP(3)-induced Ca(2+) releases in the nucleus by 55%. Microinjection of IP(3) into the nucleus of siCGB-treated PC12 cells decreased the IP(3)-dependent nuclear Ca(2+) mobilization by approximately 75%, whereas in siCGA-treated cells it remained the same as that of control cells. Given the presence of CGB in the nucleus, these results further highlight the critical contribution of nuclear CGB in the IP(3)-induced Ca(2+) release in the nucleus. 相似文献
89.
Background
Many musculoskeltal injuries in the workplace have been attributed to the repetitive loading of muscle and soft tissues. It is not disputed that muscular fatigue is a risk factor for musculoskeltal injury, however the disparity between gender with respect to muscular fatigability and rate of recovery is not well understood. Current health and safety guidelines do not account for sex differences in fatiguability and may be predisposing one gender to greater risk. The purpose of this study was to quantify the sex differences in fatigue development and recovery rate of lower and upper body musculature after repeated bouts of sustained isometric contractions.Methods
Twenty-seven healthy males (n = 12) and females (n = 15) underwent bilateral localized fatigue of either the knee extensors (male: n = 8; female: n = 8), elbow flexors (male: n = 8; female: n = 10), or both muscle groups. The fatigue protocol consisted of ten 30-second sub-maximal isometric contractions. The changes in maximum voluntary contraction (MVC), electrically evoked twitches, and motor unit activation (MUA) were assessed along with the ability to control the sustained contractions (SLP) during the fatigue protocol using a mixed four-factor repeated measures ANOVA (gender × side × muscle × time) design with significance set at p < 0.05.Results
There was a significant loss of MVC, MUA, and evoked twitch amplitude from pre- to post-fatigue in both the arms and legs. Males had greater relative loss of isometric force, a higher rate of fatigue development, and were less capable of maintaining the fatiguing contractions in the legs when compared to the females.Conclusion
The nature of the induced fatigue was a combination of central and peripheral fatigue that did not fully recover over a 45-minute period. The results appear to reflect sex differences that are peripheral, and partially support the muscle mass hypothesis for explaining differences in muscular fatigue.90.
G. W. Baeck J. M. Jeong Y. M. Yeo S.‐H. Huh J. M. Park 《Zeitschrift fur angewandte Ichthyologie》2012,28(4):677-679
The relationships are given between total length and wet weight, and between total length and standard length for 10 scorpionfishes from the south coast of Korea. 相似文献