全文获取类型
收费全文 | 1491篇 |
免费 | 43篇 |
专业分类
1534篇 |
出版年
2024年 | 5篇 |
2023年 | 16篇 |
2022年 | 36篇 |
2021年 | 71篇 |
2020年 | 24篇 |
2019年 | 53篇 |
2018年 | 47篇 |
2017年 | 40篇 |
2016年 | 47篇 |
2015年 | 80篇 |
2014年 | 75篇 |
2013年 | 113篇 |
2012年 | 104篇 |
2011年 | 93篇 |
2010年 | 49篇 |
2009年 | 51篇 |
2008年 | 66篇 |
2007年 | 51篇 |
2006年 | 79篇 |
2005年 | 62篇 |
2004年 | 53篇 |
2003年 | 42篇 |
2002年 | 33篇 |
2001年 | 15篇 |
2000年 | 17篇 |
1999年 | 14篇 |
1998年 | 7篇 |
1997年 | 10篇 |
1996年 | 9篇 |
1995年 | 10篇 |
1994年 | 14篇 |
1993年 | 9篇 |
1992年 | 7篇 |
1991年 | 11篇 |
1989年 | 4篇 |
1988年 | 8篇 |
1987年 | 6篇 |
1986年 | 4篇 |
1985年 | 17篇 |
1984年 | 6篇 |
1983年 | 7篇 |
1982年 | 6篇 |
1981年 | 9篇 |
1980年 | 11篇 |
1979年 | 7篇 |
1978年 | 5篇 |
1977年 | 4篇 |
1975年 | 4篇 |
1974年 | 4篇 |
1973年 | 6篇 |
排序方式: 共有1534条查询结果,搜索用时 15 毫秒
161.
Ahmad AS Zia S Sayeed I Ansari MA Ahmad M Salim S Yousuf S Islam F 《Biological trace element research》2005,103(1):59-68
The effect of 0.05, 0.1, and 0.2 mg sodium selenite/kg body weight ip on the activities of neurobehavioral, acetyl cholinesterase,
monoamine oxidase, and the content of dopamine and its metabolites in circadian rhythm centers of male Wistar rats was studied
after 7 d of treatment. The results show an appreciable increase in locomotion, stereo-events, distance traveled, and average
speed at the dose of 0.1 and 0.2 mg sodium selenite/kg. The data have shown hyperactivity of animals with various doses of
sodium selenite, and it was significant and dose-dependent after 3 d of treatment. The activity of acetylcholinesterase (AChE)
was inhibited dose dependently, and it was significant in preoptic area with 0.1 or 0.2 mg sodium selenite/kg. Conversely,
in the posterior hypothalamus its activity was significantly elevated with the dose of 0.2 mg sodium selenite/kg, but its
alteration in brain stem was not significant. Monoamine oxidase (MAO) activity was increased in preoptic area with the dose
of 0.1 mg sodium selenite/kg, but its alteration in posterior hypothalamus and brain stem was not significant. The content
of dopamine (DA), 3,4-dihydroxyphenyl acetic acid (DOPAC), and homovanilic acid (HVA) was elevated dose dependently and it
was significant with the doss of 0.1 and 0.2 mg sodium selenite/kg, but the content of DOPAC and HVA in posterior hypothalamus
was not significant with the dose of 0.1 mg sodium selenite/kg. 相似文献
162.
Two new prenylated anthronoids, harunmadagascarins A and B, were isolated from the stem bark of Harungana madagascariensis along with six known compounds including two anthronoids: harunganol B and harungin anthrone, one benzophenone: methyl 3-formyl-2,4-dihydroxy-6-methyl benzoate and three pentacyclic triterpenes: friedelin, lupeol and betulinic acid. Harunmadagascarins A and B were characterized as 8,9-dihydroxy-4,4-bis-(3,3-dimethylallyl)-6-methyl-2,3-(2,2-dimethylpyrano)anthrone and 8,9-dihydroxy-4,4,5-tris-(3,3-dimethylallyl)-6-methyl-2,3-(2,2-dimethylpyrano)anthrone, respectively. The structures of these secondary metabolites were determined by spectroscopic means and comparison with the published data. Methyl 3-formyl-2,4-dihydroxy-6-methyl benzoate was isolated for the first time from a plant. Harunmadagascarins A and B, harunganol B and harungin anthrone exhibited significant antioxidant activity. 相似文献
163.
Choudhary MI Musharraf SG Nawaz SA Anjum S Parvez M Fun HK Atta-ur-Rahman 《Bioorganic & medicinal chemistry》2005,13(6):1939-1944
The microbial transformation of (-)-isolongifolol (1) by using the standard two-stage fermentation technique with Fusarium lini afforded polar oxygenated metabolites: 10-oxoisolongifolol (2), 10alpha-hydroxyisolongifolol (3), and 9alpha-hydroxyisolongifolol (4). Metabolites 3 and 4 were also formed with the incubation of 1 with Aspergillus niger. All three metabolites were found to be new. Compounds 3 and 4 inhibited butyrylcholinesterase enzyme in a concentration-dependent manner with IC50 values 13.6 and 299.5 microM, respectively. Compound 3 showed un-competitive mode of inhibition against butyrylcholinesterase with Ki value 15.0 microM. The structures of metabolites 2-4 were deduced on the basis of spectroscopic techniques and single-crystal X-ray diffraction techniques. 相似文献
164.
Amor EC Villaseñor IM Ghayur MN Gilani AH Choudhary MI 《Zeitschrift für Naturforschung. C, Journal of biosciences》2005,60(1-2):67-71
The hexane extract of Syzygium samarangense (Ss.Hex) dose-dependently (10-1000 microg/ ml) relaxed the spontaneously contracting isolated rabbit jejunum. Four rare C-methylated flavonoids with a chalcone and a flavanone skeleton were isolated from Ss.Hex and were subsequently tested for spasmolytic activity. All flavonoids, identified as 2'-hydroxy-4',6'-dimethoxy-3'-methylchalcone (1), 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (2), 2',4'-dihydroxy-6'-methoxy-3'-methylchalcone (3), and 7-hydroxy-5-methoxy-6,8-dimethyl-flavanone (4), showed dose-dependent spasmolytic activity in the rabbit jejunum with IC50 values of 148.3 +/- 69.4, 77.2 +/- 43.5, 142.4 +/- 58.6 and 178.5 +/- 37.5 microg/ml (mean +/- SEM), respectively. The dihydrochalcone derivative of compound 1, 2'-hydroxy-4',6'-dimethoxy-3'-methyldihydrochalcone (5), when tested for spasmolytic activity, did not significantly relax the smooth muscle relative to the other compounds. Verapamil, a standard spasmolytic, has an IC50 value of 0.16 +/- 0.04 microg/ml. This is the first report of the relaxant activity of chalcones, specifically of compounds 1-3. 相似文献
165.
Khan T Ahmad M Nisar M Ahmad M Lodhi MA Choudhary MI 《Journal of enzyme inhibition and medicinal chemistry》2005,20(3):245-249
The ethanolic extract derived from aerial parts of an indigenous medicinal plant Paeonia emodi was screened for enzyme inhibition activities against Urease (jack bean and Bacillus pasteurii) and alpha-Chymotrypsin. The extract was also investigated for its radical scavenging activity using DPPH assay. The crude extract was found to possess significant enzyme inhibition activities against jack bean (74%) and Bacillus pasteurii (80%) urease and a moderate activity (54%) against alpha-Chymotrypsin. The extract also displayed excellent (83%) radical scavenging activity. On the basis of these results, the crude extract was subsequently fractionated into n-hexane, chloroform, ethyl acetate, n-butanol and water fractions and tested independently for the aforesaid activities. Significant inhibitory activity against urease enzyme was observed for the ethyl acetate, n-butanol and water fractions while the n-hexane and chloroform fractions were devoid of any such activity. In the alpha-Chymotrypsin enzyme inhibition studies the activity was concentrated into the ethyl acetate fraction. All the fractions displayed potent radical scavenging activity. The crude extract and fractions thereof were also subjected to total phenolic content determination. A correlation between radical scavenging capacities of extracts and total phenolic content was observed in the majority of cases. 相似文献
166.
Determination of Rhodamine 123 in cell lysate by HPLC with visible wavelength detection 总被引:3,自引:0,他引:3
Iqbal T Kinjo M Dowling TC 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2005,814(2):259-262
Rhodamine 123 (R123) is widely used to quantify P-glycoprotein (P-GP) functional efflux activity in vitro. We developed a rapid and specific high-performance liquid chromatography (HPLC) method to quantify Rhodamine 123 for use in experimental cell culture studies. The R123 standards (2.5-250 ng/mL) and quality controls (QCs) (5, 75, 200 ng/mL) were prepared in cell lysis buffer consisting of 0.75% Triton 100X and 0.2% sodium chloride. The mobile phase consisted of acetonitrile, 1.5 mM tetrabutyl ammonium bromide in 20mM sodium acetate buffer (pH 4.0) (50:20:30) delivered at a rate of 1.0 mL/min. Samples (50 microl) were injected onto a C(18) reversed-phase HPLC column with detection at 500 nm. Analyte retention times were 1.4 and 4.3 min for R123 and internal standard (R6G), respectively. Intra- and inter-day coefficients of variation were < or = 4.2%. Samples were stable for at least three freeze-thaw cycles at room temperature for 24 and 48 h. This method was used to evaluate the functional activity of P-glycoprotein in renal tubule cell models including human kidney (HK-2), Madin-Darby canine kidney (MDCK) and multi-drug resistance gene-transfected MDCK cells (MDR1-MDCK). 相似文献
167.
Curcumin, a natural, biologically active compound extracted from rhizomes of Curcuma species, has been shown to act as a biological response modifier in various disorders. We have reported previously that the dietary supplementation of curcumin enhances the activities of antioxidant and phase II metabolizing enzymes in mice (M. Iqbal, S.D. Sharma, Y. Okazaki, M. Fujisawa, S. Okada, Dietary supplementation of curcumin enhances antioxidant and phase II metabolizing enzymes in ddY mice: possible role in protection against chemical carcinogenesis and toxicity, Pharmacol and Toxicol. 92 (2003) 33_38.) and inhibits ferric nitrilotriacetate (Fe-NTA) induced oxidative injury of lipids and DNA in vitro (M. Iqbal, Y. Okazaki, S. Okada, In vitro curcumin modulates Ferric Nitrilotriacetate (Fe-NTA) and hydrogen peroxide (H(2)O(2))-induced peroxidation of microsomal membrane lipids and DNA damage, Teratogenesis Carcinogenesis and Mutagenesis Supplement 23 (2003) 151-160.). In our present study, Fe-NTA, a known complete renal carcinogen, which generate ROS in vivo, was given intraperitoneally to mice and curcumin was tested for its ability to inhibits oxidative stress and the activity of ornithine decarboxylase (ODC) as well as histopathological changes in the kidney. Substantial changes in glutathione, antioxidant enzymes as well as changes in phase II metabolizing enzymes were observed in the kidney at 12 h after treatment with Fe-NTA (9.0 mg Fe/kg body weight). Effect of oxidative stress induced by Fe-NTA were also demonstrated by the increase in lipid peroxidation as monitored by formation of thiobarbituric acid-reactive substances and 4-hydroxy-2-nonenal (HNE)-modified proteins in kidney. Likewise, the level of protein carbonyl contents, an indicator of protein oxidation was also increased after Fe-NTA administration. However, the changes in these parameters were restored to normal in curcumin-pretreated mice. The ODC activity in the kidney was significantly increased by Fe-NTA, while the increased ODC activity induced by Fe-NTA was normalized in curcumin-pretreated mice. In addition, curcumin pretreatment almost completely prevented kidney biomolecules from oxidative damage and protected the tissue against observed histopathological alterations. 相似文献
168.
A novel in vivo role for osteoprotegerin ligand in activation of monocyte effector function and inflammatory response 总被引:4,自引:0,他引:4
Seshasayee D Wang H Lee WP Gribling P Ross J Van Bruggen N Carano R Grewal IS 《The Journal of biological chemistry》2004,279(29):30202-30209
Osteoprotegerin Ligand (OPGL) is a member of the tumor necrosis factor ligand superfamily and has been shown to be involved in interactions between T cells and dendritic cells. Its role in monocyte effector function, however, has not been defined. In the present study a role for OPGL in activating monocytes/macrophages has been characterized. OPGL was found to up-regulate receptor activator of NF-kappaB (RANK) receptor expression on monocytes, regulate their effector function by inducing cytokine and chemokine secretion, activate antigen presentation through up-regulation of co-stimulatory molecule expression, and promote survival. This activation is mediated through the MAPK pathway as evidenced by activation of p38 and p42/44 MAPK and up-regulation of BCL-XL protein levels. A physiological role for OPGL in monocyte activation and effector function was tested in a model of lipopolysaccharide-induced endotoxic shock. Administration of receptor activator of NF-kappaB (RANK)-Fc to block OPGL activity in vivo was able to protect mice from death induced by sepsis, indicating a hitherto undescribed role for OPGL in monocyte function and in mediating inflammatory response. This was further tested in an animal model of inflammation-mediated arthritis. Treatment with RANK-Fc significantly ameliorated disease development and attenuated bone destruction. Thus, our study strongly suggests that administration of receptor fusion proteins to specifically block OPGL activity in vivo may result in blocking development of monocyte/macrophage-mediated diseases. 相似文献
169.
Gong CX Liu F Wu G Rossie S Wegiel J Li L Grundke-Iqbal I Iqbal K 《Journal of neurochemistry》2004,88(2):298-310
Protein phosphatase 5 (PP5) is a 58-kDa novel phosphoseryl/phosphothreonyl protein phosphatase. It is ubiquitously expressed in all mammalian tissues examined, with a high level in the brain, but little is known about its physiological substrates. We found that this phosphatase dephosphorylated recombinant tau phosphorylated with cAMP-dependent protein kinase and glycogen synthase kinase-3beta, as well as abnormally hyperphosphorylated tau isolated from brains of patients with Alzheimer's disease. The specific activity of PP5 toward tau was comparable to those reported with other protein substrates examined to date. The PP5 activity toward tau was stimulated by arachidonic acid by 30- to 45-fold. Immunostaining demonstrated that PP5 was primarily cytoplasmic in PC12 cells and in neurons of postmortem human brain tissue. A small pool of PP5 associated with microtubules. Expression of active PP5 in PC12 cells resulted in reduced phosphorylation of tau, suggesting that PP5 can also dephosphorylate tau in cells. These results suggest that PP5 plays a role in the dephosphorylation of tau and might be involved in the molecular pathogenesis of Alzheimer's disease. 相似文献
170.
Evaluation of DNA damage in a population of bats (Chiroptera) residing in an abandoned monazite mine
Ionising radiation has the ability to induce DNA damage. While the effects of high doses of radiation of short duration have been well documented, the biological effects of long-term exposure to low doses are poorly understood. This study evaluated the clastogenic effects of low dose ionising radiation on a population of bats (Chiroptera) residing in an abandoned monazite mine. Bats were sampled from two chambers in the mine, where external radiation levels measured around 20 microSv/h (low dose) and 100 microSv/h (higher dose), respectively. A control group of bats was sampled from a cave with no detectable radiation above normal background levels. The micronucleus assay was used to evaluate residual radiation damage in binucleated lymphocytes and showed that the micronucleus frequency per 500 binucleated lymphocytes was increased in the lower radiation-exposed group (17.7) and the higher radiation-exposed group (27.1) compared to the control group (5.3). This study also showed that bats exposed to radiation presented with an increased number of micronuclei per one thousand reticulocytes (2.88 and 10.75 in the lower and high radiation-exposed groups respectively) when compared to the control group (1.7). The single-cell gel electrophoresis (comet) assay was used as a means of evaluating clastogenecity of exposure to radiation at the level of individual cells. Bats exposed to radiation demonstrated increased DNA damage as shown by the length of the comet tails and showed an increase in cumulative damage. The results of the micronucleus and the comet assays indicated not only a statistically significant difference between test and control groups (P<0.001), but also a dose-dependent increase in DNA damage (P<0.001). These assays may thus be useful in evaluating the potential clastogenecity of exposure to continuous low doses of ionising radiation. 相似文献