全文获取类型
收费全文 | 321篇 |
免费 | 8篇 |
出版年
2024年 | 2篇 |
2023年 | 5篇 |
2022年 | 29篇 |
2021年 | 20篇 |
2020年 | 8篇 |
2019年 | 10篇 |
2018年 | 13篇 |
2017年 | 11篇 |
2016年 | 13篇 |
2015年 | 18篇 |
2014年 | 8篇 |
2013年 | 28篇 |
2012年 | 24篇 |
2011年 | 26篇 |
2010年 | 10篇 |
2009年 | 9篇 |
2008年 | 14篇 |
2007年 | 11篇 |
2006年 | 13篇 |
2005年 | 11篇 |
2004年 | 9篇 |
2003年 | 7篇 |
2002年 | 6篇 |
2001年 | 3篇 |
2000年 | 1篇 |
1999年 | 2篇 |
1998年 | 2篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1988年 | 1篇 |
1987年 | 3篇 |
1985年 | 1篇 |
1982年 | 1篇 |
1978年 | 1篇 |
排序方式: 共有329条查询结果,搜索用时 15 毫秒
81.
Synthesis, dihydrofolate reductase inhibition, antitumor testing, and molecular modeling study of some new 4(3H)-quinazolinone analogs 总被引:1,自引:0,他引:1
Al-Rashood ST Aboldahab IA Nagi MN Abouzeid LA Abdel-Aziz AA Abdel-Hamide SG Youssef KM Al-Obaid AM El-Subbagh HI 《Bioorganic & medicinal chemistry》2006,14(24):8608-8621
In order to produce potent new leads for anticancer drugs, a new series of quinazoline analogs was designed to resemble methotrexate (MTX, 1) structure features and fitted with functional groups believed to enhance inhibition of mammalian DHFR activity. Molecular modeling studies were used to assess the fit of these compounds within the active site of human DHFR. The synthesized compounds were evaluated for their ability to inhibit mammalian DHFR in vitro and for their antitumor activity in a standard in vitro tissue culture assay panel. Compounds 28, 30, and 31 were the most active DHFR inhibitors with IC50 values of 0.5, 0.4, and 0.4 μM, respectively. The most active antitumor agents in this study were compounds 19, 31, 41, and 47 with median growth inhibitory concentrations (GI50) of 20.1, 23.5, 26.7, and 9.1 μM, respectively. Of this series of compounds, only compound 31 combined antitumor potency with potent DHFR inhibition; the other active antitumor compounds (19, 41, and 47) all had DHFR IC50 values above 15 μM, suggesting that they might exert their antitumor potency through some other mode of action. Alternatively, the compounds could differ significantly in uptake or concentration within mammalian cells. 相似文献
82.
D. Jabborova R.Z. Sayyed A. Azimov Z. Jabbarov A. Matchanov Y. Enakiev Alaa Baazeem Ayman EL Sabagh Subhan Danish Rahul Datta 《Saudi Journal of Biological Sciences》2021,28(9):5268-5274
Ginger is used as one of the important ingredients in traditional as well as modern medicine besides as a spice. It boosts immunity and is a rich source of many biologically active substances and minerals. Although it is a medicinally important crop, its productivity is, however, affected due to poor nutrient management and therefore it requires an adequate supply of nutrients in the form of inorganic fertilizers or organic manuring, or a mixture of both. In this context, the present study was aimed to investigate the effect of mineral fertilizers on the content of mineral elements in the ginger rhizome, on soil enzyme activity, and soil properties. Lysimeter experiments were conducted at the Institute of Genetics and Plant Experimental Biology, Kibray, Tashkent region, Uzbekistan. The experiment comprised of four treatments T1 – Control, T2 - N75P50K50 kg/ha, T3 - and T4 - N100P75K75 + B3Zn6Fe6 kg/ha. The results showed that the application of N125P100K100 kg/ha increased rhizome K content by 49%, P content by 20%, and Na content by 58% as compared to control without fertilizer. While the application of N100P75K75 + B3Zn6Fe6 kg/ha showed a significant enhancement in rhizome K, Ca, P, Mg, Na, Fe, Mn, Zn, Cu, Cr, Mo, and Si contents over the control. This treatment also improved active P content by 29%, total P content by 80%, total K content 16%, and N content by 33% content, and the activities of urease, invertase, and catalase activities as compared to control of without mineral fertilizer and control respectively. Thus the application of NPK + BZnFe at the rate of 100:75:75:3:6:6 kg/ha helps in improving macroelements and microelements in the ginger rhizome and activities of soil enzymes that helps in mineral nutrition of the rhizome. 相似文献
83.
Fatmah A.M. Al-Omary Laila A. Abou-zeid Mahmoud N. Nagi El-Sayed E. Habib Alaa A.-M. Abdel-Aziz Adel S. El-Azab Sami G. Abdel-Hamide Mohamed A. Al-Omar Abdulrahman M. Al-Obaid Hussein I. El-Subbagh 《Bioorganic & medicinal chemistry》2010,18(8):2849-2863
A new series of 2,6-substituted-quinazolin-4-ones was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, and antitumor activities. Compounds 22, 33–37, 39–43, and 45 proved to be active DHFR inhibitors with IC50 range of 0.4–1.0 μM. Compound 18 showed broad-spectrum antimicrobial activity comparable to the known antibiotic gentamicin. Compounds 34 and 36 showed antitumor activity at GI50 (MG-MID) concentrations of 11.2, and 24.2 μM, respectively. Molecular modeling study including flexible alignment; electrostatic, hydrophobic mappings; and pharmacophore prediction were performed. A main featured pharmacophore model was developed which justifies the importance of the main pharmacophoric groups as well as of their relative distances. The substitution pattern and spatial considerations of the π-systems in regard to the quinazoline nucleus proved critical for biological activity. 相似文献
84.
Amal M. Youssef Edward G. Neeland Erika B. Villanueva M. Sydney White Ibrahim M. El-Ashmawy Brian Patrick Andis Klegeris Alaa S. Abd-El-Aziz 《Bioorganic & medicinal chemistry》2010,18(15):5685-5696
A novel dipyrazole ethandiamide compound and acid chloride of pyrazolo[3,4-d]pyrimidine 4(5H)-one were prepared and reacted with a number of nucleophiles. The resultant novel compounds were tested in several in vitro and in vivo assays. Three compounds inhibited the secretion of neurotoxins by human THP-1 monocytic cells at concentrations that were not toxic to these cells. They also partially inhibited both cyclooxygenase-1 and -2 isoforms. In animal studies, two compounds were notable for their anti-inflammatory activity that was comparable to that of the clinically available cyclooxygenase-2 inhibitor celecoxib. Modeling studies by using the molecular operating environment module showed comparable docking scores for the two enantiomers docked in the active site of cyclooxygenase-2. 相似文献
85.
86.
87.
88.
Harman SM Liang L Tsitouras PD Gucciardo F Heward CB Reaven PD Ping W Ahmed A Cutler RG 《Free radical biology & medicine》2003,35(10):1301-1309
To assess novel liquid chromatography/mass spectrometric methods for measuring oxidative damage to nucleic acids and lipids, we compared urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG), 5-hydroxymethyl-2'-deoxyuridine (5-OHmU), and 8-hydroxyguanosine (8-OxoG), and an isoprostane, 8-iso-prostaglandin F(2)alpha (IsopF(2)alpha) in 234 healthy men (n = 113) and women (n = 121), 80 current smokers, 96 never-smokers), and 58 ex-smokers (no tobacco use for 3 years). The 8-OHdG and 8-OxoG did not differ significantly by group; 5-OHmU was higher in smokers, compared with ex- (p <.003) and never- (p <.0001) smokers and in ex- vs. never-smokers (p =.014) at, respectively, 13.5 +/- 0.7, 11.3 +/- 1.0, and 8.7 +/- 0.3 microg/g creatinine. IsopF(2)alpha was higher in smokers, compared with ex- (p =.007) and never-smokers (p <.0001) and in ex- vs. never- smokers (p =.002) at, respectively, 1.1 +/- 0.10; 0.74 +/- 0.07, and 0.51 +/- 0.04 microg/g creatinine. There were significant correlations among all three nucleic acid adducts and between IsopF(2)alpha and both 5-OHmU and 8-OHdG. Many smokers and ex-smokers had high levels of either 5-OHmU excretion or IsopF(2)alpha excretion, but not both. We conclude that 5-OHmU and IsopF(2)alpha are more discriminating of oxidative stress from tobacco smoke than the other two compounds measured. Whether characteristic patterns of excretion of these indicators forecast differential disease risk should be explored in future research. 相似文献
89.
Huang K Yanai A Kang R Arstikaitis P Singaraja RR Metzler M Mullard A Haigh B Gauthier-Campbell C Gutekunst CA Hayden MR El-Husseini A 《Neuron》2004,44(6):977-986
In neurons, posttranslational modification by palmitate regulates the trafficking and function of signaling molecules, neurotransmitter receptors, and associated synaptic scaffolding proteins. However, the enzymatic machinery involved in protein palmitoylation has remained elusive. Here, using biochemical assays, we show that huntingtin (htt) interacting protein, HIP14, is a neuronal palmitoyl transferase (PAT). HIP14 shows remarkable substrate specificity for neuronal proteins, including SNAP-25, PSD-95, GAD65, synaptotagmin I, and htt. Conversely, HIP14 is catalytically invariant toward paralemmin and synaptotagmin VII. Exogenous HIP14 enhances palmitoylation-dependent vesicular trafficking of several acylated proteins in both heterologous cells and neurons. Moreover, interference with endogenous expression of HIP14 reduces clustering of PSD-95 and GAD65 in neurons. These findings define HIP14 as a mammalian palmitoyl transferase involved in the palmitoylation and trafficking of multiple neuronal proteins. 相似文献
90.
Al-Saleh SS 《Cell biochemistry and function》2002,20(1):1-10
Echis carinatus crude venom was fractionated into 11 protein fractions by preparative native polyacrylamide gel electrophoresis (PAGE). All fractions except fractions 5 and 10 appeared as a single band on analytical native PAGE. Purified venom fractions 1, 4, 8, 10 and 11 appeared as single bands on SDS-PAGE whereas fractions 2, 3 and 7 contained two bands and fraction 6 contained three bands. Fractions 1 and 3 exhibited basic pI (7.3 and 7.6) respectively, while fractions 2, 4, 6, 8, 10 and 11 showed an acidic pI. Amino acid analysis also showed that crude venom is rich in acidic amino acids. A significant hyperglycaemia was produced by i.p. injection of E. carinatus crude venom, after 15 min of envenomation which persisted even after 24 h. Along with hyperglycaemia there was a significant decrease of liver glycogen at 15 min and 1, 12 and 24 h. A significant decrease of plasma [pyr + lac] levels was found from 15 min to 24 h. The liver [pyr + lac] levels increased significantly after 24 h. Skeletal muscle [pyr + lac] level was significantly decreased after 24 h of envenomation. Fractions 2 and 6 produced the highest increase in plasma glucose after 12 h and fraction 7 after 24 h. The plasma insulin level was significantly decreased by these three fractions (2, 6 and 7). So it can be hypothesized that the hyperglycaemia may result from a direct effect of a venom component on plasma insulin. Fractions 7, 8 and 11 caused the highest decrease in plasma [pyr + lac] while fractions 1, 2, 3, 4 and 8 produced the most significant decrease in liver [pyr + lac]. The most significant increase in lactate dehydrogenase level was also produced by fractions 1, 2, 3, 4 and 8. 相似文献