全文获取类型
收费全文 | 440篇 |
免费 | 59篇 |
国内免费 | 6篇 |
出版年
2023年 | 4篇 |
2022年 | 6篇 |
2021年 | 14篇 |
2020年 | 9篇 |
2019年 | 11篇 |
2018年 | 13篇 |
2017年 | 7篇 |
2016年 | 14篇 |
2015年 | 20篇 |
2014年 | 19篇 |
2013年 | 30篇 |
2012年 | 34篇 |
2011年 | 37篇 |
2010年 | 29篇 |
2009年 | 28篇 |
2008年 | 29篇 |
2007年 | 25篇 |
2006年 | 16篇 |
2005年 | 16篇 |
2004年 | 15篇 |
2003年 | 14篇 |
2002年 | 9篇 |
2001年 | 9篇 |
2000年 | 9篇 |
1999年 | 4篇 |
1998年 | 2篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 4篇 |
1991年 | 4篇 |
1990年 | 7篇 |
1989年 | 4篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1986年 | 5篇 |
1985年 | 6篇 |
1984年 | 4篇 |
1983年 | 4篇 |
1982年 | 6篇 |
1981年 | 5篇 |
1979年 | 3篇 |
1978年 | 4篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1975年 | 1篇 |
1972年 | 3篇 |
1971年 | 2篇 |
1968年 | 1篇 |
1959年 | 1篇 |
排序方式: 共有505条查询结果,搜索用时 31 毫秒
471.
Aranapakam M. Venkatesan Christoph M. Dehnhardt Zecheng Chen Efren Delos Santos Osvaldo Dos Santos Matthew Bursavich Adam M. Gilbert John W. Ellingboe Semiramis Ayral-Kaloustian Gulnaz Khafizova Natasja Brooijmans Robert Mallon Irwin Hollander Larry Feldberg Judy Lucas Ker Yu Jay Gibbons Robert Abraham Tarek S. Mansour 《Bioorganic & medicinal chemistry letters》2010,20(2):653-656
This article describes the syntheses and SAR of a series of imidazolopyrimidine derivatives, which are evaluated as inhibitors of PI3-Kinase (PI3 K) and mTOR. These compounds were found to be ATP competitive with good tumor cell growth inhibition, and suppression of pathway specific biomakers such as phosphorylation of Akt at T308. 相似文献
472.
Prashant Sharma Bhavnesh Kumar Yash Gupta Neelja Singhal Vishwa Mohan Katoch Krishnamurthy Venkatesan Deepa Bisht 《Proteome science》2010,8(1):59
Background
Streptomycin (SM) is a broad spectrum antibiotic and is an important component of any anti-tuberculosis therapy regimen. Several mechanisms have been proposed to explain the emergence of resistance but still our knowledge is inadequate. Proteins form a very complex network and drugs are countered by their modification/efflux or over expression/modification of targets. As proteins manifest most of the biological processes, these are attractive targets for developing drugs, immunodiagnostics or therapeutics. The aim of present study was to analyze and compare the protein profile of whole cell extracts from Mycobacterium tuberculosis clinical isolates susceptible and resistant to SM. 相似文献473.
474.
Venkatesan RN Hsu JJ Lawrence NA Preston BD Loeb LA 《The Journal of biological chemistry》2006,281(7):4486-4494
Eukaryotic DNA polymerase (Pol) delta replicates chromosomal DNA and is also involved in DNA repair and genetic recombination. Motif A in Pol delta, containing the sequence DXXXLYPSI, includes a catalytically essential aspartic acid as well as other conserved residues of unknown function. Here, we used site-directed mutagenesis to create all 19 amino acid substitutions for the conserved Leu(612) in Motif A of Saccharomyces cerevisiae Pol delta. We show that substitutions at Leu(612) differentially affect viability, sensitivity to genotoxic agents, cell cycle progression, and replication fidelity. The eight viable mutants contained Ile, Val, Thr, Met, Phe, Lys, Asn, or Gly substitutions. Individual substitutions varied greatly in the nature and extent of attendant phenotypic deficiencies, exhibiting mutation rates that ranged from near wild type to a 37-fold increase. The L612M mutant exhibited a 7-fold elevation of mutation rate but essentially no detectable effects on other phenotypes monitored; the L612T mutant showed a nearly wild type mutation rate together with marked hypersensitivity to genotoxic agents; and the L612G and L612N strains exhibited relatively high mutation rates and severe deficits overall. We compare our results with those for homologous substitutions in prokaryotic and eukaryotic DNA polymerases and discuss the implications of our findings for the role of Leu(612) in replication fidelity. 相似文献
475.
Yogeeta SK Raghavendran HR Gnanapragasam A Subhashini R Devaki T 《Chemico-biological interactions》2006,163(1-2):160-169
Disruption of mitochondria and free radical mediated tissue injury have been reported during cardiotoxicity induced by isoproterenol (ISO), a beta-adrenergic catecholamine. The present study was designed to investigate the effect of the combination of ferulic acid (FA) and ascorbic acid (AA) on the mitochondrial damage in ISO induced cardiotoxicity. Induction of rats with ISO (150 mg/kg b.wt., i.p.) for 2 days resulted in a significant decrease in the activities of respiratory chain enzymes (NADH dehydrogenase and cytochrome c-oxidase), tricarboxylic acid cycle enzymes (isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, alpha-ketoglutarate dehydrogenase), mitochondrial antioxidants (GPx, GST, SOD, CAT, GSH), cytochromes (b, c, c1, aa3) and in the level of mitochondrial phospholipids. A marked elevation in mitochondrial lipid peroxidation, mitochondrial levels of cholesterol, triglycerides and free fatty acids were also observed in ISO intoxicated rats. Pre-co-treatment with the combination of FA (20 mg/kg b.wt.) and AA (80 mg/kg b.wt.) orally for 6 days significantly enhanced the attenuation of these functional abnormalities and restored normal mitochondrial function when compared to individual drug treated groups. Mitigation of ISO induced biochemical and morphological changes in mitochondria were more pronounced with a combination of FA and AA rather than the individual drug treated groups. Transmission electron microscopic observations also correlated with these biochemical parameters. Hence, these findings demonstrate the synergistic ameliorative potential of FA and AA on mitochondrial function during beta-adrenergic catecholamine induced cardiotoxicity and associated oxidative stress in rats. 相似文献
476.
Ramachandran G Kumar AK Swaminathan S Venkatesan P Kumaraswami V Greenblatt DJ 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2006,835(1-2):131-135
A simple and rapid high performance liquid chromatographic method for determination of efavirenz in human plasma was developed. The method involved extraction of sample with ethyl acetate and analysis using a reversed-phase C(18) column (150 mm) with UV detection. The assay was linear from 0.0625 to 10.0 microg/ml. The method was specific for efavirenz estimation and the drug was stable in plasma up to one month at -20 degrees C. The average recovery of efavirenz from plasma was 101%. Due to its simplicity, the assay can be used for pharmacokinetic studies and therapeutic drug monitoring of efavirenz. 相似文献
477.
Peripheral blood aspirates overexpressing IGF‐I via rAAV gene transfer undergo enhanced chondrogenic differentiation processes
下载免费PDF全文
![点击此处可从《Journal of cellular and molecular medicine》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Janina Frisch Patrick Orth Ana Rey‐Rico Jagadeesh Kumar Venkatesan Gertrud Schmitt Henning Madry Dieter Kohn Magali Cucchiarini 《Journal of cellular and molecular medicine》2017,21(11):2748-2758
Implantation of peripheral blood aspirates induced towards chondrogenic differentiation upon genetic modification in sites of articular cartilage injury may represent a powerful strategy to enhance cartilage repair. Such a single‐step approach may be less invasive than procedures based on the use of isolated or concentrated MSCs, simplifying translational protocols in patients. In this study, we provide evidence showing the feasibility of overexpressing the mitogenic and pro‐anabolic insulin‐like growth factor I (IGF‐I) in human peripheral blood aspirates via rAAV‐mediated gene transfer, leading to enhanced proliferative and chondrogenic differentiation (proteoglycans, type‐II collagen, SOX9) activities in the samples relative to control (reporter rAAV‐lacZ) treatment over extended periods of time (at least 21 days, the longest time‐point evaluated). Interestingly, IGF‐I gene transfer also triggered hypertrophic, osteo‐ and adipogenic differentiation processes in the aspirates, suggesting that careful regulation of IGF‐I expression may be necessary to contain these events in vivo. Still, the current results demonstrate the potential of targeting human peripheral blood aspirates via therapeutic rAAV transduction as a novel, convenient tool to treat articular cartilage injuries. 相似文献
478.
Jerome K. Geroge Priya Ranjan Prasad Verma Jayachandran Venkatesan Jin-Young Lee Dong-Han Yoon Se-Kwon Kim Sandeep Kumar Singh 《AAPS PharmSciTech》2017,18(8):2871-2888
The present study aimed for in vitro-in vivo-in silico simulation studies of experimentally designed (32-factorial) Capmul PG-8-cored, Eudragit RSPO-Lutrol F 127 nanocapsules to ferry felodipine using GastroPlus?. The in silico parameter sensitivity analysis for pharmacokinetic parameters was initially assessed to justify the preparation of felodipine-loaded nanocapsules (FLNs) with enhanced solubility to overcome the bioavailability issues of felodipine. The overall integrated desirability ranged between 0.8187 and 0.9488 for three optimized FLNs when analyzed for mean particle size, zeta potential, encapsulation efficiency, and in vitro dissolution parameters. The morphological evaluation (SEM, TEM, and AFM) demonstrated spherical nanoparticles (200–300 nm). Validated LC-MS/MS analysis demonstrated enhanced relative bioavailability (13.37-fold) of optimized FLN as compared to suspension. The simulated regional absorption of the FLN presented significant absorption from the cecum (26.3%) and ascending colon (20.1%) with overall absorption of 67.4% from the GIT tract. Furthermore, in vitro-in vivo correlation demonstrated the Wagner-Nelson method as the preferred model as compared to mechanistic and numerical deconvolution on the basis of least mean absolute prediction error, least standard error of prediction, least mean absolute error, and maximum correlation coefficient (r 2 = 0.920). The study demonstrated enhanced oral absorption of felodipine-loaded nanocapsules, and GastroPlus? was found to be an efficient simulation tool for in vitro-in vivo-in silico simulations. 相似文献
479.
Lisianthus [Eustoma grandiflorum (Raf.) Shinn] is a popular cut flower crop throughout the world, and the demand for this plant for cut flowers and potted
plants has been increasing worldwide. Recent advances in genetic engineering have enabled the transformation and regeneration
of plants to become a powerful tool for improvement of lisianthus. We have established a highly efficient plant regeneration
system and Agrobacterium-mediated genetic transformation of E. grandiflorum. The greatest shoot regeneration frequency and number of shoot buds per explant are observed on media supplemented with 6-Benzylaminopurine
(BAP) and α-Naphthalene acetic acid (NAA). We report an efficient plant regeneration system using leaf explants via organogenesis
with high efficiency of transgenic plants (15%) in culture of 11 weeks’ duration. Further ectopic expression of two MADS box
genes, LMADS1-M from lily (Lilium longiflorum) and OMADS1 from orchid (Oncidium Gower Ramsey), was performed in E. grandiflorum. Conversion of second whorl petals into sepal-like structures and alteration of third whorl stamen formation were observed
in the transgenic E. grandiflorum plants ectopically expressing 35S::LMADS1-M. 35S::OMADS1 transgenic E. grandiflorum plants flowered significantly earlier than non-transgenic plants. This is the first report on the ectopic expression of two
MADS box genes in E. grandiflorum using a simple and highly efficient gene transfer protocol. Our results reveal the potential for floral modification in E. grandiflorum through genetic transformation. 相似文献