全文获取类型
收费全文 | 413篇 |
免费 | 34篇 |
出版年
2021年 | 6篇 |
2019年 | 4篇 |
2018年 | 7篇 |
2017年 | 4篇 |
2016年 | 8篇 |
2015年 | 21篇 |
2014年 | 14篇 |
2013年 | 20篇 |
2012年 | 21篇 |
2011年 | 22篇 |
2010年 | 17篇 |
2009年 | 18篇 |
2008年 | 27篇 |
2007年 | 16篇 |
2006年 | 19篇 |
2005年 | 12篇 |
2004年 | 19篇 |
2003年 | 12篇 |
2002年 | 14篇 |
2001年 | 15篇 |
2000年 | 16篇 |
1999年 | 16篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1996年 | 8篇 |
1995年 | 6篇 |
1994年 | 7篇 |
1993年 | 5篇 |
1992年 | 6篇 |
1991年 | 9篇 |
1990年 | 11篇 |
1989年 | 7篇 |
1988年 | 6篇 |
1987年 | 5篇 |
1986年 | 3篇 |
1985年 | 8篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1977年 | 6篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1929年 | 1篇 |
排序方式: 共有447条查询结果,搜索用时 328 毫秒
101.
102.
In the active centre of pancreatic phospholipase A2 His48 is at hydrogen-bonding distance to Asp99. This Asp-His couple is assumed to act together with a water molecule as a catalytic triad. Asp99 is also linked via an extended hydrogen bonding system to the side chains of Tyr52 and Tyr73. To probe the function of the fully conserved Asp99, Tyr52 and Tyr73 residues in phospholipase A2, the Asp99 residue was replaced by Asn, and each of the two tyrosines was separately replaced by either a Phe or a Gln. The catalytic and binding properties of the Phe52 and Phe73 mutants did not change significantly relative to the wild-type enzyme. This rules out the possibility that either one of the two Tyr residues in the wild-type enzyme can function as an acyl acceptor or proton donor in catalysis. The Gln73 mutant could not be obtained in any significant amounts probably due to incorrect folding. The Gln52 mutant was isolated in low yield. This mutant showed a large decrease in catalytic activity while its substrate binding was nearly unchanged. The results suggest a structural role rather than a catalytic function of Tyr52 and Tyr73. Substitution of asparagine for aspartate hardly affects the binding constants for both monomeric and micellar substrate analogues. Kinetic characterization revealed that the Asn99 mutant has retained no less than 65% of its enzymatic activity on the monomeric substrate rac 1,2-dihexanoyldithio-propyl-3-phosphocholine, probably due to the fact that during hydrolysis of monomeric substrate by phospholipase A2 proton transfer is not the rate-limiting step.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
103.
104.
105.
106.
107.
Koppe MJ Oyen WJ Bleichrodt RP Hendriks T Verhofstad AA Goldenberg DM Boerman OC 《Cancer immunology, immunotherapy : CII》2006,55(1):47-55
Background: Inhibition of the COX-2 enzyme has been shown to have a radiosensitizing effect in epithelial cancers. The aim of this study
was to investigate whether the efficacy of radioimmunotherapy (RIT) using 131I-labeled anti-CEA monoclonal antibody MN-14 could be enhanced by co-administration of the selective COX-2 inhibitor Parecoxib
in mice with small volume (1–3 mm) peritoneal carcinomatosis of colonic origin. Methods: First, the efficacy of 14 daily injections of Parecoxib monotherapy (0 – 0.2 – 1.0 – 5.0 – 25.0 mg/kg) was determined in
mice with intraperitoneal LS174T xenografts. Second, the influence of Parecoxib (1.0 or 5.0 mg/kg) on the biodistribution
of 125I-MN-14 was assessed. Finally, the efficacy of RIT alone [125 μCi 131I-MN-14/mouse ≈ 1/4 of the maximal tolerated dose (MTD)] was compared with that of Parecoxib monotherapy and RIT combined
with daily injections of Parecoxib (1.0 or 5.0 mg/kg). Results: Parecoxib had no measurable antitumor effect up to the highest dose level (25 mg/kg). Parecoxib had no effect on the uptake
of 125I-MN-14 in the intraperitoneal tumor xenografts or on normal tissue distribution. Median survival of the control mice and
the mice treated with Parecoxib monotherapy (1.0 or 5.0 mg/kg) was 48.5 days, 52 days and 52 days (P=0.47). RIT alone significantly delayed the growth of the intraperitoneal xenografts resulting in a median survival of 87 days
(P<0.0001). Mice treated with RIT + Parecoxib at 1.0 or 5.0 mg/kg had a median survival of 73.5 days and 76 days, respectively,
which was not statistically different from survival after RIT alone (P=0.15). Conclusion: The COX-2 inhibitor Parecoxib does not enhance the therapeutic efficacy of RIT of experimental small volume peritoneal carcinomatosis
of colonic origin. 相似文献
108.
Polarisation, key to good localisation 总被引:2,自引:0,他引:2
van Beest M Robben JH Savelkoul PJ Hendriks G Devonald MA Konings IB Lagendijk AK Karet F Deen PM 《Biochimica et biophysica acta》2006,1758(8):1126-1133
Polarisation of cells is crucial for vectorial transport of ions and solutes. In literature, however, proteins specifically targeted to the apical or basolateral membrane are often studied in non-polarised cells. To investigate whether these data can be extrapolated to expression in polarised cells, we studied several membrane-specific proteins. In polarised MDCK cells, the Aquaporin-2 water channel resides in intracellular vesicles and apical membrane, while the vasopressin-type 2 receptor, anion-exchanger 1 (AE1) protein and E-Cadherin mainly localise to the basolateral membrane. In non-polarised MDCK cells, however, Aquaporin-2 localises, besides plasma membrane, mainly in the Golgi complex, while the others show a dispersed staining throughout the cell. Moreover, while AQP2 mutants in dominant nephrogenic diabetes insipidus are missorted to different organelles in polarised cells, they all predominantly localise to the Golgi complex in non-polarised MDCK cells. Additionally, the maturation of V2R, and likely its missorting, is affected in transiently-transfected compared to stably-transfected cells. In conclusion, we show that the use of stably-transfected polarised cells is crucial in interpreting the processing and the localisation of membrane targeted proteins. 相似文献
109.
110.
Gerard van der Velde Rob S. E. W. Leuven Dirk Platvoet Karolina Bacela Mark A. J. Huijbregts Harrie W. M. Hendriks Dirk Kruijt 《Biological invasions》2009,11(9):2043-2054
Predatory behaviour seems to be more frequent in invasive gammaridean species than in native ones. This results in the exclusion
of other, mostly native gammaridean species and a change in benthic communities. The present study analysed the influence
of environmental factors (water temperature) and morphological factors (sex, body parts involved in catching and holding prey)
on the predatory behaviour of Dikerogammarus villosus. A diet study of invasive relatives of D. villosus showed that predation intensity is especially high in spring and summer, that is, at increasing and high temperatures. Experiments
with D. villosus in climate rooms at various temperatures, using the native Gammarus fossarum as prey, showed that the average predation rate by both sexes gradually increased over the temperature range from 5 to 30°C.
Natural mortality during the experiments was negligible compared to losses due to predation. At each temperature, the predation
rate by females was lower than that by males. Males showed a steep allometric growth of body parts involved in the process
of catching and holding prey, compared to females at increasing body size in a number of measurements. This may explain the
difference in predatory behaviour between males and females, which plays a role in intraguild predation a supposed mechanism
for species displacement. 相似文献