全文获取类型
收费全文 | 143篇 |
免费 | 17篇 |
出版年
2018年 | 1篇 |
2017年 | 1篇 |
2015年 | 1篇 |
2014年 | 1篇 |
2013年 | 3篇 |
2012年 | 1篇 |
2011年 | 2篇 |
2010年 | 2篇 |
2009年 | 1篇 |
2008年 | 20篇 |
2007年 | 8篇 |
2006年 | 4篇 |
2005年 | 7篇 |
2004年 | 2篇 |
2003年 | 7篇 |
2002年 | 4篇 |
2001年 | 3篇 |
2000年 | 4篇 |
1999年 | 3篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1994年 | 3篇 |
1993年 | 4篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1989年 | 2篇 |
1987年 | 1篇 |
1986年 | 4篇 |
1985年 | 4篇 |
1984年 | 1篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1979年 | 2篇 |
1977年 | 5篇 |
1976年 | 6篇 |
1975年 | 7篇 |
1974年 | 4篇 |
1973年 | 3篇 |
1972年 | 4篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1969年 | 2篇 |
1968年 | 1篇 |
1967年 | 3篇 |
1966年 | 2篇 |
1965年 | 2篇 |
1961年 | 1篇 |
1960年 | 1篇 |
排序方式: 共有160条查询结果,搜索用时 15 毫秒
71.
72.
73.
74.
Synthesis, chiral chromatographic separation, and biological activities of the enantiomers of 10,10-dimethylhuperzine A 总被引:1,自引:0,他引:1
Rajendran V Prakash KR Ved HS Saxena A Doctor BP Kozikowski AP 《Bioorganic & medicinal chemistry letters》2000,10(21):2467-2469
(+/-)-10,10-Dimethylhuperzine A (2, DMHA) has been synthesized, and its enantiomers have been separated using chiral HPLC. (-)-DMHA inhibits AChE with a Ki value approaching that of (-)-huperzine A, whereas (+)-DMHA shows no AChE inhibitory activity. On the other hand, both enantiomers are equally potent against glutamate-induced neurotoxicity when tested in neurons. 相似文献
75.
An incoherent elastic neutron scattering study of the molecular dynamics of native human butyrylcholinesterase and its “aged” soman-inhibited conjugate revealed a significant change in molecular flexibility on an angstrom-nanosecond scale as a function of temperature. The results were related to the stability of each state as established previously by differential scanning calorimetry. A striking relationship was found between the denaturation behavior and the molecular flexibility of the native and inhibited enzymes as a function of temperature. This was reflected in a quantitative correlation between the atomic mean-square displacements on an angstrom-nanosecond scale determined by neutron spectroscopy and the calorimetric specific heat. By the application of a simple two-state model that describes the transition from a folded to a denatured state, the denaturation temperatures of the native and the inhibited enzyme were correctly extracted from the atomic mean-square displacements. Furthermore, the transition entropy and enthalpy extracted from the model fit of the neutron data were, within the experimental accuracy, compatible with the values determined by differential scanning calorimetry. 相似文献
76.
Valiyaveettil M Alamneh Y Biggemann L Soojhawon I Doctor BP Nambiar MP 《Biochemical and biophysical research communications》2010,403(1):97-13
Paraoxonase 1 (PON1) has been described as an efficient catalytic bioscavenger due to its ability to hydrolyze organophosphates (OPs) and chemical warfare nerve agents (CWNAs). It is the future most promising candidate as prophylactic medical countermeasure against highly toxic OPs and CWNAs. Most of the studies conducted so far have been focused on the hydrolyzing potential of PON1 against nerve agents, sarin, soman, and VX. Here, we investigated the hydrolysis of tabun by PON1 with the objective of comparing the hydrolysis potential of human and rabbit serum purified and recombinant human PON1. The hydrolysis potential of PON1 against tabun, sarin, and soman was evaluated by using an acetylcholinesterase (AChE) back-titration Ellman method. Efficient hydrolysis of tabun (100 nM) was observed with ∼25-40 mU of PON1, while higher concentration (80-250 mU) of the enzyme was required for the complete hydrolysis of sarin (11 nM) and soman (3 nM). Our data indicate that tabun hydrolysis with PON1 was ∼30-60 times and ∼200-260 times more efficient than that with sarin and soman, respectively. Moreover, the catalytic activity of PON1 varies from source to source, which also reflects their efficiency of hydrolyzing different types of nerve agents. Thus, efficient hydrolysis of tabun by PON1 suggests its promising potential as a prophylactic treatment against tabun exposure. 相似文献
77.
Porotto M Doctor L Carta P Fornabaio M Greengard O Kellogg GE Moscona A 《Journal of virology》2006,80(19):9837-9849
Hendra virus (HeV) is a recently identified paramyxovirus that is fatal in humans and could be used as an agent of bioterrorism. The HeV receptor-binding protein (G) is required in order for the fusion protein (F) to mediate fusion, and analysis of the triggering/activation of HeV F by G should lead to strategies for interfering with this key step in viral entry. HeV F, once triggered by the receptor-bound G, by analogy with other paramyxovirus F proteins, undergoes multistep conformational changes leading to a six-helix bundle (6HB) structure that accomplishes fusion of the viral and cellular membranes. The ectodomain of paramyxovirus F proteins contains two conserved heptad repeat regions (HRN and HRC) near the fusion peptide and the transmembrane domains, respectively. Peptides derived from the HRN and HRC regions of F are proposed to inhibit fusion by preventing F, after the initial triggering step, from forming the 6HB structure that is required for fusion. HeV peptides have previously been found to be effective at inhibiting HeV fusion. However, we found that a human parainfluenza virus 3 F-peptide is more effective at inhibiting HeV fusion than the comparable HeV-derived peptide. 相似文献
78.
79.
Chilukuri N Duysen EG Parikh K Sun W Doctor BP Lockridge O Saxena A 《Chemico-biological interactions》2008,175(1-3):327-331
Human serum butyrylcholinesterase (Hu BChE) is a promising therapeutic against the toxicity of chemical warfare nerve agents, pesticide intoxication, and cocaine overdose. However, its widespread application is hampered by difficulties in large-scale production of the native protein from human plasma and/or availability as a recombinant protein suitable for use in vivo. This limitation may be resolved by in vivo delivery and expression of the Hu BChE gene. In this study, recombinant (r) adenoviruses (Ads) encoding full-length and truncated rHu BChEs were tested for in vivo expression in mice. Mice injected with these rAds intraperitoneally failed to express rHu BChE. However, a single tail vein injection of both rAds resulted in persistent high serum levels of rHu BChE in BChE knockout mice, which peaked on days 4/5 at 377+/-162U/ml for full-length rHu BChE and 574+/-143U/ml for truncated rHu BChE. These activity levels are orders of magnitude higher than 1.9U/ml of mouse BChE present in wild-type mouse serum. Thereafter, rHu BChE levels dropped rapidly and very little or no activity was detected in the serum 10 days post-virus administration. In conclusion, the present study demonstrates the potential of rAd-mediated Hu BChE gene therapy to counteract multiple lethal doses of chemical warfare nerve agent toxicity. 相似文献
80.
Nageswararao Chilukuri Ellen G. Duysen Kalpana Parikh Wei Sun Bhupendra P. Doctor Oksana Lockridge Ashima Saxena 《Chemico-biological interactions》2008,175(1-3):327
Human serum butyrylcholinesterase (Hu BChE) is a promising therapeutic against the toxicity of chemical warfare nerve agents, pesticide intoxication, and cocaine overdose. However, its widespread application is hampered by difficulties in large-scale production of the native protein from human plasma and/or availability as a recombinant protein suitable for use in vivo. This limitation may be resolved by in vivo delivery and expression of the Hu BChE gene. In this study, recombinant (r) adenoviruses (Ads) encoding full-length and truncated rHu BChEs were tested for in vivo expression in mice. Mice injected with these rAds intraperitoneally failed to express rHu BChE. However, a single tail vein injection of both rAds resulted in persistent high serum levels of rHu BChE in BChE knockout mice, which peaked on days 4/5 at 377 ± 162 U/ml for full-length rHu BChE and 574 ± 143 U/ml for truncated rHu BChE. These activity levels are orders of magnitude higher than 1.9 U/ml of mouse BChE present in wild-type mouse serum. Thereafter, rHu BChE levels dropped rapidly and very little or no activity was detected in the serum 10 days post-virus administration. In conclusion, the present study demonstrates the potential of rAd-mediated Hu BChE gene therapy to counteract multiple lethal doses of chemical warfare nerve agent toxicity. 相似文献