全文获取类型
收费全文 | 567篇 |
免费 | 25篇 |
国内免费 | 2篇 |
出版年
2024年 | 1篇 |
2023年 | 6篇 |
2022年 | 7篇 |
2021年 | 39篇 |
2020年 | 22篇 |
2019年 | 21篇 |
2018年 | 35篇 |
2017年 | 27篇 |
2016年 | 19篇 |
2015年 | 25篇 |
2014年 | 33篇 |
2013年 | 48篇 |
2012年 | 51篇 |
2011年 | 42篇 |
2010年 | 18篇 |
2009年 | 23篇 |
2008年 | 20篇 |
2007年 | 29篇 |
2006年 | 17篇 |
2005年 | 29篇 |
2004年 | 25篇 |
2003年 | 10篇 |
2002年 | 9篇 |
2001年 | 2篇 |
2000年 | 4篇 |
1999年 | 5篇 |
1998年 | 1篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 1篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1984年 | 2篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1962年 | 1篇 |
排序方式: 共有594条查询结果,搜索用时 15 毫秒
91.
Ehsan Ullah Mughal Amina Sadiq Shahzad Murtaza Hummera Rafique Muhammad Naveed Zafar Tauqeer Riaz Bilal Ahmad Khan Abdul Hameed Khalid Mohammed Khan 《Bioorganic & medicinal chemistry》2017,25(1):100-106
The present study describes efficient and facile syntheses of varyingly substituted 3-thioaurones from the corresponding 3-oxoaurones using Lawesson’s reagent and phosphorous pentasulfide. In comparison, the latter methodology was proved more convenient, giving higher yields and required short and simple methodology. The structures of synthetic compounds were unambiguously elucidated by IR, MS and NMR spectroscopy. All synthetic compounds were screened for their inhibitory potential against in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Molecular docking studies were also performed in order to examine their binding interactions with AChE and BChE human proteins. Both studies revealed that some of these compounds were found to be good inhibitors against AChE and BChE. 相似文献
92.
Nawab John Dar Javeed Ahmad Bhat Naresh Kumar Satti Parduman Raj Sharma Abid Hamid Muzamil Ahmad 《Molecular neurobiology》2017,54(7):5061-5073
Withania somnifera has immense pharmacologic and clinical uses. Owing to its similar pharmacologic activity as that of Korean Ginseng tea, it is popularly called as Indian ginseng. In most cases, extracts of this plant have been evaluated against various diseases or models of disease. However, little efforts have been made to evaluate individual constituents of this plant for neurodegenerative disorders. Present study was carried out to evaluate Withanone, one of the active constituents of Withania somnifera against NMDA-induced excitotoxicity in retinoic acid, differentiated Neuro2a cells. Cells were pre-treated with 5, 10 and 20 μM doses of Withanone and then exposed to 3-mM NMDA for 1 h. MK801, a specific NMDA receptor antagonist, was used as positive control. The results indicated that NMDA induces significant death of cells by accumulation of intracellular Ca2+, generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential, crashing of Bax/Bcl-2 ratio, release of cytochrome c, increased caspase expression, induction of lipid peroxidation as measured by malondialdehyde levels and cleavage of poly(ADP-ribose) polymerase-1 (Parp-1), which is indicative of DNA damage. All these parameters were attenuated with various doses of Withanone pre-treatment. These results suggest that Withanone may serve as potential neuroprotective agent. 相似文献
93.
Abid Ali Khaskheli Aysun Cebeci Aydin Sana Jawaid Muhammad Ali Surhio Hassan Imran Afridi 《Bioscience, biotechnology, and biochemistry》2017,81(10):2002-2008
Conjugated linoleic acid (CLA) has attracted as novel type of fatty acids having unusual health-promoting properties such as anticarcinogenic and antiobesitic effects. The present work employed castor oil as substrate for one-pot production of CLA using washed cells of Lactobacillus plantarum (L. plantarum) and lipases as catalysts. Among the screened lipases, the lipase Rhizopus oryzae (ROL) greatly assisted resting cells to produce CLA. Mass spectral analysis of the product showed that two major isomers of CLA were produced in the reaction mixture i.e. cis-9, trans-11 56.55% and trans-10, cis-12 43.45%. Optimum factors for CLA synthesis were found as substrate concentration (8 mg/mL), pH (6.5), washed cell concentration (12% w/v), and incubation time of 20 h. Hence, the combination of ROL with L. plantarum offers one pot production of CLA selectively using castor oil as a cost-effective substrate. 相似文献
94.
Bleomycin (BLM), an antitumor antibiotic, is currently used during anticancer therapy. The therapeutic efficiency of BLM for the treatment of malignant tumors is related to its ability to cleave DNA. However, little is known about the biological activity of the glycannic moiety in BLM-induced cytotoxicity. In this study, cell death induced by BLM-A2 and deglycosylated BLM-A2 was studied in a laryngeal carcinoma cell line (HEp-2 cells). Our results indicate that HEp-2 cells showed morphological and biochemical changes associated with apoptosis in the presence of low concentrations of BLM-A2. In contrast, the same changes, except activation of caspase-3 and internucleosomal digestion of genomic DNA, were observed when cells were exposed to high concentrations of deglycosylated BLM-A2. These observations indicate that the glycannic moiety from the bleomycin molecule has important biological effects on the cytotoxicity of the drug. 相似文献
95.
A number of new imine derivatives of 5-amino-1, 3, 4-thiadiazole-2-thiol have been synthesized, and their anti-depressant activity was tested using imipramine as reference drug. Two compounds namely 5-{[1-(4-chlorophenyl)-3-(4-methoxy-phenyl)prop-2-en-1-ylidene]-amino}-5-benzylthio-1, 3,4 -thiadiazole 4i(b) and 5-{[1-(4-chlorophenyl)-3-(4-dimethyl-aminophenyl)-prop-2-en-1-ylidene]amino}-5-benzylthio-1,3,4-thiadiazole 4i(c) have shown significant anti-depressant activity, which decreased immobility time by 77.99% and 76.26% compared to the standard imipramine (82%). All the compounds in the series have passed neurotoxicity tests. 相似文献
96.
The root extract of Operculina turpethum (OTE) has been used as an anti-inflammatory, purgative, and hepato-protective agent. N-Nitrosodimethylamine (NDMA) is a potent hepatotoxin that induces fibrosis of the liver. In the present study, we examined the therapeutic effects of OTE root extract against NDMA-induced hepatotoxicity and clastogenicity in rats. Hepatic fibrosis was induced in adult male albino rats through serial intraperitoneal administrations of NDMA at a concentration of 10 mg/kg body weight on three consecutive days of each week over a period of three weeks. A group of rats received OTE orally in doses of 75, 150 and 200 mg/kg body weight at 5 h after the administration of NDMA. The controls and treated animals were sacrificed on days-7, 14 and 21 after the start of the administration of NDMA. The progression of hepatic fibrosis as well as the amelioration effect of OTE was evaluated through histopathologically as well as by immunohistochemical staining for the activation of hepatic stellate cells. Alterations in serum and liver biochemical parameters and LDH isoenzymes were also studied. Serial administration of NDMA resulted in well formed fibrosis in the liver and induction of micronuclei in the bone marrow cells. Staining of α-SMA demonstrated activated stellate cells from day-7 onwards which was dramatically increased on day-21. An elevation of micronuclei count, liver function enzymes, serum hydroxyproline levels and LDH isoenzymes 4 and 5 were also observed. All these changes were remarkably reduced in OTE administered animals and fibrogenesis was completely absent. Our results suggest that OTE has hepatoprotective and anti-clastogenic effects against NDMA-induced hepatic fibrosis. Therefore OTE may be used as a hepatoprotective agent against various liver diseases including toxic liver injury. 相似文献
97.
Sfar S Abid A Mahfoudh W Ouragini H Ouechtati F Abdelhak S Chouchane L 《Molecular biology reports》2009,36(4):661-667
Hereditary multiple exostoses (HME) is an autosomal dominant orthopaedic disorder most frequently caused by mutations in the
EXT1 gene. The aim of the present study is to determine the underlying molecular defect of HME in two multigenerational Tunisian
families with 21 affected members and to examine the degree of intrafamilial variability. Linkage analysis was performed using
three microsatellite markers encompassing the EXT1 locus and mutation screening was carried out by direct sequencing. In family 1, evidence for linkage to EXT1 was obtained on the basis of a maximum LOD score of 4.26 at θ = 0.00 with D8S1694 marker. Sequencing of the EXT1 revealed a heterozygous G > T transversion (c.1019G>T) in exon 2, leading to a missense mutation at the codon 340 (p.Arg340Leu).
In family 2 we identified a novel heterozygous 1 bp deletion in the exon 1 (c.529_531delA) leading to a premature codon stop
and truncated EXT1 protein expression (p.Lys177LysfsX15). This mutation was associated with the evidence of an intrafamilial
clinical variability and considered to be a novel disease-causing mutation in the EXT1 gene. These findings provide additional support for the involvement of EXT1 gene in the HME disease. 相似文献
98.
Molecular cloning of fungal xylanases: an overview 总被引:1,自引:0,他引:1
Xylanases have received great attention in the development of environment-friendly technologies in the paper and pulp industry.
Their use could greatly improve the overall lignocellulosic materials for the generation of liquid fuels and chemicals. Fungi
are widely used as xylanase producers and are generally considered as more potent producers of xylanases than bacteria and
yeasts. Large-scale production of xylanases is facilitated with the advent of genetic engineering. Recent breakthroughs in
genomics have helped to overcome the problems such as limited enzyme availability, substrate scope, and operational stability.
Genes encoding xylanases have been cloned in homologous and heterologous hosts with the objectives of overproducing the enzyme
and altering its properties to suit commercial applications. Owing to the industrial importance of xylanases, a significant
number of studies are reported on cloning and expression of the enzymes during the last few years. We, therefore, have reviewed
recent knowledge regarding cloning of fungal xylanase genes into various hosts for heterologous production. This will bring
an insight into the current status of cloning and expression of the fungal xylanases for industrial applications. 相似文献
99.
Francesco Marchetti Massimo Bergamin Susanna Bosi Riaz Khan Erminio Murano Stefano Norbedo 《Carbohydrate polymers》2009,75(4):670-676
Polysaccharides are widely used as carriers in the field of drug delivery. We present a methodology to obtain water soluble drug-conjugates based on scleroglucan. Selective C-6 halogenation gives access to C-6 esters; conjugates between methotrexate and scleroglucan are described, potentially useful for antitumour therapy or in rheumatoid arthritis treatment. 相似文献
100.
Folate is an essential cofactor for normal cellular proliferation and tissue regeneration. Alcohol-associated folate deficiency is common, primarily due to intestinal malabsorption, the mechanism of which needs attention. The aim of the present study was to evaluate the regulatory events of folate transport in experimental alcohol ingestion. For this, male Wistar rats were fed 1 g/kg body weight/day ethanol (20% solution) orally for 3 months and folate transport was studied in isolated intestinal epithelial cells across the crypt-villus axis. The role of different signaling pathways in folate transport regulation was evaluated independently to that of reduced folate carrier (RFC) expression. The results showed that differentiated cells of villus possess high folate uptake activity as compared to mid villus and crypt base cells. During chronic ethanol ingestion, decrease in transport was observed all along the crypt-villus axis but was more pronounced at proliferating crypt base stem cells. Studying the effect of modulators of signaling pathways revealed the folate transport system to be under the regulation of cAMP-dependent protein kinase A (PKA), the activity of which was observed to decrease upon alcohol ingestion. In addition, protein kinase C might have a role in folate transport regulation during alcoholic conditions. The deregulation in the folate transport system was associated with a decrease in RFC expression, which may result in lower transport efficiency observed at absorptive surface in alcohol-fed rats. The study highlights the role that perturbed regulatory pathways and RFC expression play in the decreased folate transport at brush border surface during alcohol ingestion. 相似文献