全文获取类型
收费全文 | 779篇 |
免费 | 38篇 |
出版年
2023年 | 2篇 |
2022年 | 11篇 |
2021年 | 23篇 |
2020年 | 13篇 |
2019年 | 15篇 |
2018年 | 28篇 |
2017年 | 19篇 |
2016年 | 30篇 |
2015年 | 31篇 |
2014年 | 49篇 |
2013年 | 60篇 |
2012年 | 73篇 |
2011年 | 60篇 |
2010年 | 28篇 |
2009年 | 31篇 |
2008年 | 29篇 |
2007年 | 35篇 |
2006年 | 31篇 |
2005年 | 30篇 |
2004年 | 26篇 |
2003年 | 22篇 |
2002年 | 17篇 |
2001年 | 5篇 |
2000年 | 11篇 |
1999年 | 8篇 |
1998年 | 5篇 |
1997年 | 6篇 |
1996年 | 5篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 13篇 |
1991年 | 10篇 |
1990年 | 9篇 |
1989年 | 5篇 |
1988年 | 6篇 |
1987年 | 3篇 |
1986年 | 6篇 |
1985年 | 6篇 |
1984年 | 6篇 |
1983年 | 5篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 6篇 |
1978年 | 5篇 |
1977年 | 4篇 |
1976年 | 2篇 |
1975年 | 3篇 |
1974年 | 6篇 |
1968年 | 2篇 |
排序方式: 共有817条查询结果,搜索用时 31 毫秒
61.
Vinod R. Hegde Scott Borges Haiyan Pu Mahesh Patel Vincent P. Gullo Bonnie Wu Paul Kirschmeier Michael J. Williams Vincent Madison Thierry Fischmann Tze-Ming Chan 《Bioorganic & medicinal chemistry letters》2010,20(4):1384-1387
Several analogs of aristolochic acids were isolated and derivatized into their lactam derivatives to study their inhibition in CDK2 assay. The study helped to derive some conclusions about the structure–activity relation around the phenanthrin moiety. Semi-synthetic aristolactam 21 showed good activity with inhibition IC50 of 35 nM in CDK2 assay. The activity of this compound was comparable to some of the most potent synthetic compounds reported in the literature. 相似文献
62.
63.
Elevations in reactive oxygen species are implicated in many disease states and cause systolic and diastolic myocardial dysfunction. To understand the underlying cellular dysfunction, we characterised the effects of H?O? on [Ca(2+)](i) handling and contractility in the rat ventricular myocyte. This was achieved using patch clamping, [Ca(2+)](i) measurement using Fluo-3, video edge detection and confocal microscopy. All experiments were performed at 37°C. 200 μM H?O? resulted in a 44% decrease in the [Ca(2+)](i) transient amplitude, a 30% increase in diastolic [Ca(2+)](i) and an 18% decrease in the rate of systolic Ca(2+) removal. This was associated with a 61% reduction in systolic shortening, a contracture of 3 μm and a 42% increase in relaxation time respectively. The decrease in the [Ca(2+)](i) transient amplitude could be explained by a 27% decrease in SR Ca(2+) content. This, in turn results from a 22% decrease of SERCA activity. The decreased SR Ca(2+) content also provides a mechanism for a reduction in [Ca(2+)](i) spark frequency with no evidence for a Ca(2+) independent modification of ryanodine receptor open probability. We conclude that decreased SERCA activity is the major factor responsible for the changes of the systolic [Ca(2+)](i) transient. 相似文献
64.
Pakala SB Gorla P Pinjari AB Krovidi RK Baru R Yanamandra M Merrick M Siddavattam D 《Applied microbiology and biotechnology》2007,73(6):1452-1462
A soil bacterium capable of utilizing methyl parathion as sole carbon and energy source was isolated by selective enrichment
on minimal medium containing methyl parathion. The strain was identified as belonging to the genus Serratia based on a phylogram constructed using the complete sequence of the 16S rRNA. Serratia sp. strain DS001 utilized methyl parathion, p-nitrophenol, 4-nitrocatechol, and 1,2,4-benzenetriol as sole carbon and energy sources but could not grow using hydroquinone
as a source of carbon. p-Nitrophenol and dimethylthiophosphoric acid were found to be the major degradation products of methyl parathion. Growth on
p-nitrophenol led to release of stoichiometric amounts of nitrite and to the formation of 4-nitrocatechol and benzenetriol.
When these catabolic intermediates of p-nitrophenol were added to resting cells of Serratia sp. strain DS001 oxygen consumption was detected whereas no oxygen consumption was apparent when hydroquinone was added to
the resting cells suggesting that it is not part of the p-nitrophenol degradation pathway. Key enzymes involved in degradation of methyl parathion and in conversion of p-nitrophenol to 4-nitrocatechol, namely parathion hydrolase and p-nitrophenol hydroxylase component “A” were detected in the proteomes of the methyl parathion and p-nitrophenol grown cultures, respectively. These studies report for the first time the existence of a p-nitrophenol hydroxylase component “A”, typically found in Gram-positive bacteria, in a Gram-negative strain of the genus
Serratia.
Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users. 相似文献
65.
Novel steroidal saponins, Sch 725737 and Sch 725739, from a marine starfish, Novodinia antillensis 总被引:1,自引:0,他引:1
Yang SW Chan TM Buevich A Priestley T Crona J Reed J Wright AE Patel M Gullo V Chen G Pramanik B Chu M 《Bioorganic & medicinal chemistry letters》2007,17(20):5543-5547
Bioassay-guided fractionation of an active fraction from an extract of a marine starfish, Novodinia antillensis, led to the isolation and identification of two new saponins, Sch 725737 (1) and Sch 725739 (2). Compound 1 was identified as the NaV1.8 inhibitor with IC(50) of approximately 9 microM. The purification and the structure elucidation of these two saponins are described. 相似文献
66.
Panchal M 《Bioinformatics (Oxford, England)》2007,23(4):509-510
ANeCA is a fully automated implementation of Nested Clade Phylogeographic Analysis. This was originally developed by Templeton and colleagues, and has been used to infer, from the pattern of gene sequence polymorphisms in a geographically structured population, the historical demographic processes that have shaped its evolution. Until now it has been necessary to perform large parts of the procedure manually. We provide a program that will take data in Nexus sequential format, and directly output a set of inferences. The software also includes TCS v1.18 and GeoDis v2.2 as part of automation. Availability: The software is available free of charge from http://www.rubic.rdg.ac.uk/~mahesh/software.html. The program is written in Java and requires the Java 1.4 Runtime Environment (or later) to run. The source code is included in the package, and includes the source from TCS and GeoDis. ANeCA, TCS and GeoDis are released under the GNU General Public License. 相似文献
67.
Satralkar MK Khare PV Keny VL Chhakchhuak V Kasture MS Shivagaje AJ Iyyer SB Joshi DS 《Chronobiology international》2007,24(1):21-30
The sensitivity of the circadian photoreceptors mediating entrainment of the eclosion rhythm and phase shifts of oviposition rhythm of the high altitude (HA) strain of Drosophila ananassae originating from Badrinath (5123 m above sea level) in the Himalayas was compared with the low altitude (LA) strain from Firozpur (179 m above sea level). Reduced photic sensitivity of the HA strain is regarded as the result of natural selection, which led to the weakening of the coupling mechanism between the circadian pacemaker and light at the high altitude of origin. The present study was designed to determine whether or not the photic entrainment of the oviposition rhythm of the HA strain of D. ananassae is also altered by the high altitude of its origin, and the results are compared with those of the LA strain. The effects of light intensity on the phase angle difference (Ψ), degree of rhythmicity (R), the percent oviposition in photophase, the threshold light intensity (i.e., the intensity at which stable entrainment occurred), and the saturation light intensity (i.e., the intensity beyond which the values of Ψ or amplitude of rhythm remained unaltered) were determined. Entrainment was studied in light-dark cycles in which the light intensity of 12 h of photophase varied from 1 to 1000 lux, and complete darkness prevailed in all scotophases. The oviposition rhythm of the HA strain was arrhythmic from 1 to 90 lux, weakly rhythmic at 95 lux, but rhythmic at or above 100 lux, while that of the LA strain was weakly rhythmic at 1 lux but rhythmic at or above 2 lux. Oviposition of the HA strain occurred mostly in the photophase, while that of the LA strain occurred in the scotophase; as a result, the oviposition medians of the HA strain were around the subjective forenoons while those of the LA strain were around the subjective evenings. The percent of oviposition in photophase increased from 68 to 98 in the HA strain and from 5 to 33 in the LA strain as light intensity increased from 1 to 1000 lux. In the HA strain, the Ψ values were significantly less and values of R and percent oviposition in photophase were significantly more than those of the LA strain at each level of light intensity. Threshold and saturation intensities for Ψ were 100 and 700 lux, respectively, for the HA strain, but just 2 and 45 lux, respectively, for the LA strain. The saturation intensity for R was 650 and 700 lux for the HA and LA strains, respectively. These results extend the confirmation that the reduced photic sensitivity of the HA strain might have been acquired through natural selection in response to environmental conditions at the high altitude of its origin. 相似文献
68.
Vaish Swati Parveen Reshma Rajneesh Singh Nootan Gupta Divya Basantani Mahesh Kumar 《Journal of plant research》2022,135(6):823-852
Journal of Plant Research - Plant glutathione S-transferases are an ancient protein superfamily having antioxidant activity. These proteins are primarily involved in diverse plant functions such as... 相似文献
69.
Packiarajan M Marzabadi MR Desai M Lu Y Noble SA Wong WC Jubian V Chandrasena G Wolinsky TD Zhong H Walker MW Wiborg O Andersen K 《Bioorganic & medicinal chemistry letters》2011,21(18):5436-5441
The structure-activity relationship of a series of tricyclic-sulfonamide compounds 11-32 culminating in the discovery of N-[trans-4-(4,5-dihydro-3,6-dithia-1-aza-benzo[e]azulen-2-ylamino)-cyclohexylmethyl]-methanesulfonamide (15, Lu AA33810) is reported. Compound 15 was identified as a selective and high affinity NPY5 antagonist with good oral bioavailability in mice (42%) and rats (92%). Dose dependent inhibition of feeding was observed after i.c.v. injection of the selective NPY5 agonist ([cPP(1-7),NPY(19-23),Ala(31),Aib(32),Gln(34)]-hPP). In addition, ip administration of Lu AA33810 (10 mg/kg) produced antidepressant-like effects in a rat model of chronic mild stress. 相似文献
70.
Mahesh R Devadoss T Pandey DK Bhatt S 《Bioorganic & medicinal chemistry letters》2011,21(4):1253-1256
A novel series of 3-ethoxyquinoxalin-2-carboxamides were designed as per the pharmacophoric requirements of 5-HT3 receptor antagonist using ligand-based approach. The desired carboxamides were synthesized from the key intermediate, 3-ethoxyquinoxalin-2-carboxylic acid by coupling with appropriate amines in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl) and 1-hydroxybenzotriazole (HOBt). The 5-HT3 receptor antagonism was evaluated in longitudinal muscle myenteric plexus preparation from guinea pig ileum against 5-HT3 agonist, 2-methy-5-HT, which was expressed in the form of pA2 values. Compound 6h (3-ethoxyquinoxalin-2-yl)(4-methylpiperazin-1-yl)methanone was found to be the most active compound, which expressed a pA2 value of 7.7. In forced swim test, the compounds with higher pA2 value exhibited good anti-depressant-like activity and compounds with lower pA2 value failed to show activity as compared to the vehicle-treated group. 相似文献