全文获取类型
收费全文 | 421篇 |
免费 | 45篇 |
出版年
2023年 | 2篇 |
2021年 | 4篇 |
2019年 | 2篇 |
2018年 | 7篇 |
2017年 | 2篇 |
2016年 | 5篇 |
2015年 | 8篇 |
2014年 | 12篇 |
2013年 | 20篇 |
2012年 | 27篇 |
2011年 | 32篇 |
2010年 | 24篇 |
2009年 | 20篇 |
2008年 | 20篇 |
2007年 | 26篇 |
2006年 | 41篇 |
2005年 | 19篇 |
2004年 | 19篇 |
2003年 | 23篇 |
2002年 | 27篇 |
2001年 | 10篇 |
2000年 | 10篇 |
1999年 | 13篇 |
1998年 | 5篇 |
1997年 | 3篇 |
1996年 | 4篇 |
1995年 | 2篇 |
1994年 | 5篇 |
1993年 | 4篇 |
1992年 | 5篇 |
1991年 | 5篇 |
1990年 | 5篇 |
1989年 | 5篇 |
1988年 | 5篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1981年 | 4篇 |
1980年 | 6篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1976年 | 6篇 |
1975年 | 3篇 |
1974年 | 1篇 |
1973年 | 3篇 |
1969年 | 1篇 |
排序方式: 共有466条查询结果,搜索用时 15 毫秒
461.
462.
Hasan Ishtayeh Margarita Galves Tania T. Barnatan Yevgeny Berdichevsky Fatima Amer-Sarsour Metsada Pasmanik-Chor Itzhak Braverman Sergiu C. Blumen Avraham Ashkenazi 《Aging cell》2023,22(10):e13949
Autophagy is an intracellular degradative process with an important role in cellular homeostasis. Here, we show that the RNA binding protein (RBP), heterogeneous nuclear ribonucleoprotein Q (HNRNPQ)/SYNCRIP is required to stimulate early events in autophagosome biogenesis, in particular the induction of VPS34 kinase by ULK1-mediated beclin 1 phosphorylation. The RBPs HNRNPQ and poly(A) binding protein nuclear 1 (PABPN1) form a regulatory network that controls the turnover of distinct autophagy-related (ATG) proteins. We also show that oculopharyngeal muscular dystrophy (OPMD) mutations engender a switch from autophagosome stimulation to autophagosome inhibition by impairing PABPN1 and HNRNPQ control of the level of ULK1. The overexpression of HNRNPQ in OPMD patient-derived cells rescues the defective autophagy in these cells. Our data reveal a regulatory mechanism of autophagy induction that is compromised by PABPN1 disease mutations, and may thus further contribute to their deleterious effects. 相似文献
463.
464.
Avraham Geier Rina Hemi Michal Haimsohn Rachel Beery Zvi Malik Avraham Karasik 《In vitro cellular & developmental biology. Animal》1994,30(5):336-343
Summary In the present study, we investigated the ability of epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1),
and insulin to protect the human breast cancer cell line MDA-231 from death induced by the antitumor drug actinomycin D (ACT-D).
ACT-D is an inhibitor of RNA and protein synthesis, and its cytotoxicity may result due to continuous depletion in some vital
protein molecules. Cell death was induced in the MDA-231 cells by either continuous exposure to a low dose of ACT-D (0.2μg/ml), or by a short-time exposure to a high dose of ACT-D (2μg/ml) and further culturing in the absence of the drug. Cell death was evaluated by the trypan blue dye exclusion test, the
release of lactic dehydrogenase into the culture medium, and the depletion in the cellular ATP content. EGF and IGF-1, each
at an optimal concentration of 20 ng/ml, enhanced substantially survival of cells exposed either to a low or a high dose of
ACT-D. The combination of EGF (10 ng/ml) and IGF-1 (10 ng/ml) had an additive survival effect, which proposes that each of
the growth factors enhanced survival by a distinct pathway. Insulin up to 40 ng/ml had no effect on cell survival. Pretreatment
of the cells for 1 to 5 h with EGF and IGF-1 protected cells from the cytotoxic effect of ACT-D. Exposure of the cells to
2μg/ml of ACT-D for 1 h resulted in a drastic inhibition in uridine incorporation and only in a slight inhibition in leucine
incorporation. Further incubation in the absence of ACT-D resulted in a continuous decrease in uridine and in leucine incorporation,
either in the absence or presence of the growth factors. However, EGF and IGF-1, but not insulin, attenuated significantly
this continuous decrease. We assume that EGF and IGF-1 protect cell viability by a mechanism that maintains a critical level
of some vital protein molecule above the critical level at which cells die. Our finding that EGF and IGF-1 induced resistance
to ACT-D suggests that growth factors may be involved in the mechanism of drug resistance. 相似文献
465.
James Hury Uma Nagaswamy Maia Larios-Sanz George E. Fox 《Origins of life and evolution of the biosphere》2006,36(4):421-429
The modern ribosome and its component RNAs are quite large and it is likely that at an earlier time they were much smaller. Hence, not all regions of the modern ribosomal RNAs (rRNA) are likely to be equally old. In the work described here, it is hypothesized that the oldest regions of the RNAs will usually be highly integrated into the machinery. When this is the case, an examination of the interconnectivity between local RNA regions can provide insight to the relative age of the various regions. Herein, we describe an analysis of all known long-range RNA/RNA interactions within the 23S rRNA and between the 23S rRNA and the 16S rRNA in order to assess the interconnectivity between the usual Domains as defined by secondary structure. Domain V, which contains the peptidyl transferase center is centrally located, extensively connected, and therefore likely to be the oldest region. Domain IV and Domain II are extensively interconnected with both themselves and Domain V. A portion of Domain IV is also extensively connected with the 30S subunit and hence Domain IV may be older than Domain II. These results are consistent with other evidence relating to the relative age of RNA regions. Although the relative time of addition of the GTPase center can not be reliably deduced it is pointed out that the development of this may have dramatically affected the progenotes that preceded the last common ancestor. 相似文献
466.