全文获取类型
收费全文 | 158篇 |
免费 | 11篇 |
专业分类
169篇 |
出版年
2023年 | 2篇 |
2022年 | 1篇 |
2021年 | 4篇 |
2020年 | 3篇 |
2019年 | 4篇 |
2018年 | 3篇 |
2017年 | 2篇 |
2016年 | 6篇 |
2015年 | 5篇 |
2014年 | 5篇 |
2013年 | 15篇 |
2012年 | 7篇 |
2011年 | 13篇 |
2010年 | 11篇 |
2009年 | 8篇 |
2008年 | 11篇 |
2007年 | 9篇 |
2006年 | 12篇 |
2005年 | 10篇 |
2004年 | 7篇 |
2003年 | 6篇 |
2002年 | 6篇 |
2001年 | 2篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1992年 | 3篇 |
1991年 | 4篇 |
1990年 | 1篇 |
1988年 | 1篇 |
1979年 | 1篇 |
排序方式: 共有169条查询结果,搜索用时 11 毫秒
21.
22.
Mohamed Jawed Ahsan Jeyabalan Govindasamy Habibullah Khalilullah Govind Mohan James P. Stables Christophe Pannecouque Eric De Clercq 《Bioorganic & medicinal chemistry letters》2012,22(23):7029-7035
A series of 43, 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues (D01–D43) were analysed using Petra, Osiris, Molinspiration and ALOGPS (POMA) to identify pharmacophore, toxicity prediction, lipophilicity and bioactivity. All the compounds were evaluated for anti-HIV activity. 3-(4-Chlorophenyl)-N-(4-fluorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (D07) was found to be the most active with IC50 > 4.83 μM and CC50 4.83 μM. 3-(4-Fluorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carbothioamide (D41) was found to be the most active compound against bacterial strains with MIC of 4 μg/ml, comparable to the standard drug ciprofloxacin while 3-(4-methoxyphenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (D38) was found to be the most active compound against fungal strains with MIC 2–4 μg/ml, however less active than standard fluconazole. Toxicities prediction by Osiris were well supported and experimentally verified with exception of some compounds. In anticonvulsant screening, 3-(4-fluorophenyl)-N-(4-chlorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (D09) showed maximum activity showing 100% (4/4, 0.25–0.5 h) and 75% (3/4, 1.0 h) protection against minimal clonic seizure test without any toxicity. 相似文献
23.
Lakshmanan Govindasamy Thomas Kukar Wei Lian Brenda Pedersen Yunrong Gu Mavis Agbandje-McKenna Shouguang Jin Robert McKenna Donghai Wu 《Journal of structural biology》2004,146(3):1269-424
We report the crystal structure of a binary complex of human peroxisomal carnitine acetyltransferase and the substrate l-carnitine, refined to a resolution of 1.8 Angstrom with an R(factor) value of 18.9% (R(free)=22.3%). L-carnitine binds to a preformed pocket in the active site tunnel of carnitine acetyltransferase aligned with His(322). The quaternary nitrogen of carnitine forms a pi-cation interaction with Phe(545), while Arg(497) forms an electrostatic interaction with the negatively charged carboxylate group. An extensive hydrogen bond network also occurs between the carboxylate group and Tyr(431), Thr(444), and a bound water molecule. Site-directed mutagenesis and kinetic characterization reveals that Tyr(431), Thr(444), Arg(497), and Phe(545) are essential for high affinity binding of L-carnitine. 相似文献
24.
Barrese AA Genis C Fisher SZ Orwenyo JN Kumara MT Dutta SK Phillips E Kiddle JJ Tu C Silverman DN Govindasamy L Agbandje-McKenna M McKenna R Tripp BC 《Biochemistry》2008,47(10):3174-3184
This paper examines the functional mechanism of thioxolone, a compound recently identified as a weak inhibitor of human carbonic anhydrase II by Iyer et al. (2006) J. Biomol. Screening 11, 782-791 . Thioxolone lacks sulfonamide, sulfamate, or hydroxamate functional groups that are typically found in therapeutic carbonic anhydrase (CA) inhibitors, such as acetazolamide. Analytical chemistry and biochemical methods were used to investigate the fate of thioxolone upon binding to CA II, including Michaelis-Menten kinetics of 4-nitrophenyl acetate esterase cleavage, liquid chromatography-mass spectrometry (LC-MS), oxygen-18 isotope exchange studies, and X-ray crystallography. Thioxolone is proposed to be a prodrug inhibitor that is cleaved via a CA II zinc-hydroxide mechanism known to catalyze the hydrolysis of esters. When thioxolone binds in the active site of CA II, it is cleaved and forms 4-mercaptobenzene-1,3-diol via the intermediate S-(2,4-thiophenyl)hydrogen thiocarbonate. The esterase cleavage product binds to the zinc active site via the thiol group and is therefore the active CA inhibitor, while the intermediate is located at the rim of the active-site cavity. The time-dependence of this inhibition reaction was investigated in detail. Because this type of prodrug inhibitor mechanism depends on cleavage of ester bonds, this class of inhibitors may have advantages over sulfonamides in determining isozyme specificity. A preliminary structure-activity relationship study with a series of structural analogues of thioxolone yielded similar estimates of inhibition constants for most compounds, although two compounds with bromine groups at the C1 carbon of thioxolone were not inhibitory, suggesting a possible steric effect. 相似文献
25.
Chung Ill-Min Rekha Kaliyaperumal Rajakumar Govindasamy Thiruvengadam Muthu 《Bioprocess and biosystems engineering》2018,41(11):1665-1677
Bioprocess and Biosystems Engineering - Glucosinolates (GSLs) and phenolic compounds (PCs) are biologically active and involved in the defense reaction of plants; these compounds have a beneficial... 相似文献
26.
27.
Fisher SZ Maupin CM Budayova-Spano M Govindasamy L Tu C Agbandje-McKenna M Silverman DN Voth GA McKenna R 《Biochemistry》2007,46(11):2930-2937
Human carbonic anhydrase II (HCA II) is a zinc-metalloenzyme that catalyzes the reversible interconversion of CO2 and HCO3-. The rate-limiting step of this catalysis is the transfer of a proton between the Zn-bound solvent molecule and residue His64. In order to fully characterize the active site structural features implicated in the proton transfer mechanism, the refined X-ray crystal structure of uncomplexed wild type HCA II to 1.05 A resolution with an Rcryst value of 12.0% and an Rfree value of 15.1% has been elucidated. This structure provides strong clues as to the pathway of the intramolecular proton transfer between the Zn-bound solvent and His64. The structure emphasizes the role of the solvent network, the unique positioning of solvent molecule W2, and the significance of the dual conformation of His64 in the active site. The structure is compared with molecular dynamics (MD) simulation calculations of the Zn-bound hydroxyl/His64+ (charged) and the Zn-bound water/His64 (uncharged) HCA II states. A comparison of the crystallographic anisotropic atomic thermal parameters and MD simulation root-mean-square fluctuation values show excellent agreement in the atomic motion observed between the two methods. It is also interesting that the observed active site solvent positions in the crystal structure are also the most probable positions of the solvent during the MD simulations. On the basis of the comparative study of the MD simulation results, the HCA II crystal structure observed is most likely in the Zn-bound water/His64 state. This conclusion is based on the following observations: His64 is mainly (80%) orientated in an inward conformation; electron density omit maps infer that His64 is not charged in an either inward or outward conformation; and the Zn-bound solvent is most likely a water molecule. 相似文献
28.
Minna J. Hsu Jin-Fu Lin Govindasamy Agoramoorthy 《Primates; journal of primatology》2017,58(2):323-334
Group fission in non-human primates has long been proposed to result from interactions between ecological and social factors. Several studies have documented possible causes for group fission, but its proximate causes and ultimate adaptive values are not yet fully understood. We have examined the existing hypotheses on fission from long-term demographic data of Formosan macaques inhabiting the lowland rainforest at Mt Longevity, Taiwan. Five cases of fission occurred in four social groups. We have recorded two types of fission: one involving the separation of a high-ranking adult male and multiple adult females, the other initiated by adult females from main groups. Five adult females immigrated and emigrated a few times between the main and branch groups (oscillation) in three fission events. Data presented in this study are consistent with the prediction that low-ranking females split from main groups when their fitness costs increase due to ecological pressure or population growth. However, their reproductive success may decrease after fission due to a high rate of intra-group competition. Nevertheless, it is beneficial for males to be involved in fission since this increases reproductive benefits by decreasing the sex ratio in small newly formed groups. 相似文献
29.
Govindasamy Kamaraj Shankar R. Chinchkar Lingala Rajendra Villuppanoor Alwar Srinivasan 《Indian journal of microbiology》2009,49(2):161-168
The present study was undertaken to study the immune response in calves vaccinated with Brucella abortus strain 19, infectious bovine rhinotracheitis (IBR) vaccines in monovalent form and combined vaccine containing both antigen.
The seroconversion of monovalent and combined vaccines was tested in seronegative cattle calves. IBR vaccine alone and combination
with live Brucella abortus S19 vaccine elicited an anamnestic response on day 60 post booster but started declining from day 90 onwards against IBR.
B. abortus S19 alone and in combination with IBR vaccine gave more than 2 log protection in mice two weeks post challenge. Fluorescence
polarization assay analysis with sera samples of calves vaccinated with B. abortus S19 monovalent vaccine alone and in combination with IBR vaccine revealed the presence of B. abortus antibodies. The components of the combined vaccine did not show any evidence of interference in the development of immunity.
This combined vaccine may provide economical and affordable biological for the control of brucellosis and IBR. 相似文献
30.