全文获取类型
收费全文 | 391篇 |
免费 | 35篇 |
出版年
2017年 | 5篇 |
2016年 | 7篇 |
2015年 | 10篇 |
2014年 | 8篇 |
2013年 | 5篇 |
2012年 | 11篇 |
2011年 | 17篇 |
2010年 | 8篇 |
2009年 | 7篇 |
2008年 | 5篇 |
2007年 | 13篇 |
2006年 | 11篇 |
2005年 | 11篇 |
2004年 | 19篇 |
2002年 | 7篇 |
2001年 | 11篇 |
2000年 | 9篇 |
1999年 | 13篇 |
1998年 | 16篇 |
1997年 | 11篇 |
1996年 | 11篇 |
1995年 | 12篇 |
1994年 | 6篇 |
1993年 | 6篇 |
1992年 | 14篇 |
1991年 | 8篇 |
1990年 | 7篇 |
1989年 | 8篇 |
1988年 | 5篇 |
1987年 | 10篇 |
1986年 | 6篇 |
1985年 | 14篇 |
1984年 | 5篇 |
1983年 | 6篇 |
1982年 | 6篇 |
1980年 | 5篇 |
1979年 | 6篇 |
1978年 | 7篇 |
1977年 | 10篇 |
1976年 | 8篇 |
1975年 | 5篇 |
1974年 | 5篇 |
1973年 | 6篇 |
1972年 | 5篇 |
1971年 | 4篇 |
1970年 | 7篇 |
1969年 | 4篇 |
1968年 | 3篇 |
1967年 | 4篇 |
1966年 | 3篇 |
排序方式: 共有426条查询结果,搜索用时 171 毫秒
321.
322.
E. Posner 《BMJ (Clinical research ed.)》1969,3(5662):107-109
323.
324.
325.
C Polychronakos H J Guyda B I Posner 《Biochemical and biophysical research communications》1988,157(2):632-638
The insulin-like growth factor II (IGF-II) and glycoprotein lysosomal enzymes containing mannose 6-phosphate (M6P) bind with high affinity to two separate sites on the same receptor molecule (Morgan et al. Nature 329:301). The addition of free M6P significantly increases the affinity of some preparations of the M6P/IGF-II receptor (M6P/IGF-II-R) for IGF-II. We conducted this study to test the hypothesis that this effect is the result of displacement of M6P-related ligands that inhibit IGF-II binding. First we found that although M6P caused a 66% increase in the binding of IGF-II to microsomes prepared from IM9 cells, it had no effect, under identical conditions, on binding to receptor on the surface of intact cells. Secondly, extensive washing of rat liver microsomes in the presence of 3 mM M6P, followed by removal of the M6P by further washing, abolished the effect by raising binding to levels seen in the presence of M6P. M6P, then, had no additional effect. Finally, when IGF-II-affinity purified receptor was repurified by ultracentrifugation on a sucrose gradient, binding to the pure receptor peak was not affected by M6P. We conclude that there is no intrinsic positive cooperativity between free M6P and the IGF-II-binding site of the M6P/IGF-II-R. The reported M6P-induced increase in IGF-II binding appears to be due to the displacement of contaminating inhibitory endogenous ligands. 相似文献
326.
327.
Xue Bao Martijn C Koorengevel Marian J A Groot Koerkamp Amir Homavar Amrah Weijn Stefan Crielaard Mike F Renne Joseph H Lorent Willie JC Geerts Michal A Surma Muriel Mari Frank C P Holstege Christian Klose Anton I P M de Kroon 《The EMBO journal》2021,40(20)
Phosphatidylcholine (PC) is an abundant membrane lipid component in most eukaryotes, including yeast, and has been assigned multiple functions in addition to acting as building block of the lipid bilayer. Here, by isolating S. cerevisiae suppressor mutants that exhibit robust growth in the absence of PC, we show that PC essentiality is subject to cellular evolvability in yeast. The requirement for PC is suppressed by monosomy of chromosome XV or by a point mutation in the ACC1 gene encoding acetyl‐CoA carboxylase. Although these two genetic adaptations rewire lipid biosynthesis in different ways, both decrease Acc1 activity, thereby reducing average acyl chain length. Consistently, soraphen A, a specific inhibitor of Acc1, rescues a yeast mutant with deficient PC synthesis. In the aneuploid suppressor, feedback inhibition of Acc1 through acyl‐CoA produced by fatty acid synthase (FAS) results from upregulation of lipid synthesis. The results show that budding yeast regulates acyl chain length by fine‐tuning the activities of Acc1 and FAS and indicate that PC evolved by benefitting the maintenance of membrane fluidity. 相似文献
328.
329.
330.
Bryan T. Mott Ran He Xiaochun Chen Jennifer M. Fox Curt I. Civin Ravit Arav-Boger Gary H. Posner 《Bioorganic & medicinal chemistry》2013,21(13):3702-3707
We recently reported the anti-cancer and anti-cytomegalovirus (CMV) activity of artemisinin-derived trioxane diphenylphosphate dimer 838. To probe the relationship between chemical structure and anti-CMV and anti-cancer activities, we now report synthesis and evaluation of a series of eight new dimer phosphate ester analogs of 838. This series of novel molecules was screened against human foreskin fibroblasts (HFFs) infected with CMV and against the human Jurkat T cell acute lymphoblastic leukemia cell line. This SAR study confirms the very high anti-CMV and anti-cancer potencies of dimer diphenyl phosphate ester 838 without its being toxic to normal cells. 相似文献