全文获取类型
收费全文 | 1089篇 |
免费 | 87篇 |
国内免费 | 2篇 |
出版年
2023年 | 12篇 |
2022年 | 13篇 |
2021年 | 42篇 |
2020年 | 27篇 |
2019年 | 26篇 |
2018年 | 32篇 |
2017年 | 38篇 |
2016年 | 49篇 |
2015年 | 53篇 |
2014年 | 59篇 |
2013年 | 101篇 |
2012年 | 79篇 |
2011年 | 80篇 |
2010年 | 50篇 |
2009年 | 33篇 |
2008年 | 54篇 |
2007年 | 34篇 |
2006年 | 47篇 |
2005年 | 49篇 |
2004年 | 37篇 |
2003年 | 26篇 |
2002年 | 21篇 |
2001年 | 17篇 |
2000年 | 12篇 |
1999年 | 16篇 |
1998年 | 10篇 |
1997年 | 4篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1992年 | 6篇 |
1991年 | 4篇 |
1990年 | 7篇 |
1989年 | 8篇 |
1988年 | 9篇 |
1987年 | 5篇 |
1986年 | 8篇 |
1985年 | 8篇 |
1984年 | 4篇 |
1983年 | 8篇 |
1982年 | 5篇 |
1981年 | 6篇 |
1980年 | 11篇 |
1979年 | 10篇 |
1978年 | 4篇 |
1977年 | 4篇 |
1974年 | 4篇 |
1973年 | 5篇 |
1971年 | 5篇 |
1969年 | 6篇 |
1966年 | 4篇 |
排序方式: 共有1178条查询结果,搜索用时 568 毫秒
121.
The Asian citrus psyllid, Diaphorina citri Kuwayama, is a worldwide pest of citrus, which vectors the putative causal pathogen of huanglongbing. Current management practices warrant continuous monitoring of field populations for insecticide resistance. Baseline activities of acetylcholinesterase (AChE), general esterase, and glutathione S-transferase as well as sensitivity of AChE to selected organophosphate and carbamate insecticides were established for a susceptible laboratory strain (Lab) and compared with several field populations of D. citri from Florida. The specific activity of AChE in various D. citri populations ranged from 0.77 to 1.29 microM min(-1) mg of protein(-1); the Lab strain was characterized by the highest activity. Although reduced AChE sensitivity was observed in the Lab strain compared with field populations, overlap of 95% confidence intervals of I50 values (concentration required for 50% AChE activity inhibition) suggests no significant difference in AChE sensitivity among all populations tested for a given insecticide. There was no significant evidence of target site insensitivity in field populations that were exposed to the selected organophosphate and carbamate insecticides tested. The specific activity of general esterase and glutathione S-transferase was lowest in the Lab strain and was generally comparable to that of the field populations evaluated. The current data provide a mode-of-action specific baseline for future monitoring of resistance to organophosphate and carbamate insecticides in populations of D. citri. 相似文献
122.
123.
A micropropagation protocol for Bacopa monniera (L.) Wettst., a medicinally important plant, has been developed. Direct organogenesis without callus formation was induced
by culturing node, internode and leaf explants on growth regulator free Murashige and Skoog (MS) medium. MS medium supplemented
with an antibiotic trimethoprim (TMP) and a fungicide bavistin (BVN) produced axillary shoots from node and adventitious shoot
buds on the surface of all explants. The combination of 200 mg dm−3 TMP and 200 mg dm−3 BVN induced the optimum frequency of shoot formation as well as shoot number. Presence of both TMP and BVN induced multiple
axillary shoot formation from the nodal segments and this ability was maintained for four subcultures. 相似文献
124.
S. P. Tiwari Deepika Yadav Pradeep Kumar D. K. Chauhan 《Plant Systematics and Evolution》2012,298(4):723-730
A comparative study of Taxodium distichum
(L.) Rich. and Taxodium mucronatum
Ten. was carried out on the basis of pollen morphology and wood anatomy by light and scanning electron microscopy. We describe
a detailed analysis of the anatomical characteristics of the wood, including the tracheids, ray parenchyma, axial parenchyma
and number of cross-field pits. Palynological characters were also studied to reveal the shape, size and ultrastructure of
the pollen grains. These studies give taxonomic support for the recognition of T. distichum and T. mucronatum as two different species. 相似文献
125.
Moon HJ Tiwari MK Singh R Kang YC Lee JK 《Applied and environmental microbiology》2012,78(9):3079-3086
Ribitol dehydrogenase from Zymomonas mobilis (ZmRDH) catalyzes the conversion of ribitol to d-ribulose and concomitantly reduces NAD(P)(+) to NAD(P)H. A systematic approach involving an initial sequence alignment-based residue screening, followed by a homology model-based screening and site-directed mutagenesis of the screened residues, was used to study the molecular determinants of the cofactor specificity of ZmRDH. A homologous conserved amino acid, Ser156, in the substrate-binding pocket of the wild-type ZmRDH was identified as an important residue affecting the cofactor specificity of ZmRDH. Further insights into the function of the Ser156 residue were obtained by substituting it with other hydrophobic nonpolar or polar amino acids. Substituting Ser156 with the negatively charged amino acids (Asp and Glu) altered the cofactor specificity of ZmRDH toward NAD(+) (S156D, [k(cat)/K(m)(,NAD)]/[k(cat)/K(m)(,NADP)] = 10.9, where K(m)(,NAD) is the K(m) for NAD(+) and K(m)(,NADP) is the K(m) for NADP(+)). In contrast, the mutants containing positively charged amino acids (His, Lys, or Arg) at position 156 showed a higher efficiency with NADP(+) as the cofactor (S156H, [k(cat)/K(m)(,NAD)]/[k(cat)/K(m)(,NADP)] = 0.11). These data, in addition to those of molecular dynamics and isothermal titration calorimetry studies, suggest that the cofactor specificity of ZmRDH can be modulated by manipulating the amino acid residue at position 156. 相似文献
126.
Tiwari MK Singh RK Singh R Jeya M Zhao H Lee JK 《The Journal of biological chemistry》2012,287(23):19429-19439
The medium-chain dehydrogenase/reductase (MDR) superfamily consists of a large group of enzymes with a broad range of activities. Members of this superfamily are currently the subject of intensive investigation, but many aspects, including the zinc dependence of MDR superfamily proteins, have not yet have been adequately investigated. Using a density functional theory-based screening strategy, we have identified a strictly conserved glycine residue (Gly) in the zinc-dependent MDR superfamily. To elucidate the role of this conserved Gly in MDR, we carried out a comprehensive structural, functional, and computational analysis of four MDR enzymes through a series of studies including site-directed mutagenesis, isothermal titration calorimetry, electron paramagnetic resonance (EPR), quantum mechanics, and molecular mechanics analysis. Gly substitution by other amino acids posed a significant threat to the metal binding affinity and activity of MDR superfamily enzymes. Mutagenesis at the conserved Gly resulted in alterations in the coordination of the catalytic zinc ion, with concomitant changes in metal-ligand bond length, bond angle, and the affinity (K(d)) toward the zinc ion. The Gly mutants also showed different spectroscopic properties in EPR compared with those of the wild type, indicating that the binding geometries of the zinc to the zinc binding ligands were changed by the mutation. The present results demonstrate that the conserved Gly in the GHE motif plays a role in maintaining the metal binding affinity and the electronic state of the catalytic zinc ion during catalysis of the MDR superfamily enzymes. 相似文献
127.
Rao VK Chhikara BS Tiwari R Shirazi AN Parang K Kumar A 《Bioorganic & medicinal chemistry letters》2012,22(1):410-414
A number of 2-substituted tetrahydroindazolones were synthesized by three-component condensation reaction of 1,3-diketones, substituted hydrazines, benzaldehydes, and Yb(OTf)(3) as a catalyst in [bmim][BF(4)] ionic liquid using a simple, efficient, and economical one-pot method. The synthesized tetrahydroindazolones were evaluated for inhibition of cell proliferation of human colon carcinoma (HT-29), human ovarian adenocarcinoma (SK-OV-3), and c-Src kinase activity. 3,4-Dichlorophenyl tetrahydroindazolone derivative (15) inhibited the cell proliferation of HT-29 and SK-OV-3 cells by 62% and 58%, respectively. 2,3-Diphenylsubstituted tetrahydroindazolone derivatives, inhibited the cell proliferation of HT-29 cells by 65-72% at a concentration of 50 μM. In general, the tetrahydroindazolones showed modest inhibition of c-Src kinase where 4-tertbutylphenyl- and 3,4-dichlorophenyl- derivatives showed the inhibition of c-Src kinase with IC(50) values of 35.1 and 50.7 μM, respectively. 相似文献
128.
Tiwari D Kamble J Chilgunde S Patil P Maru G Kawle D Bhartiya U Joseph L Vanage G 《Mutation research》2012,743(1-2):83-90
Bisphenol A (BPA) is a well-known endocrine disruptor (ED) which represents a major toxicological and public health concern due to its widespread exposure to humans. BPA has been reported to induce DNA adduct and aneuploidy in rodents. Recent studies in humans depicted its association with recurrent miscarriages and male infertility due to sperm DNA damage indicating that BPA might have genotoxic activity. Hence, the present study was designed to determine genotoxic and mutagenic effects of BPA using in-vivo and in-vitro assays. The adult male and female rats were orally administered with various doses of BPA (2.4 μg, 10 μg, 5mg and 50mg/kgbw) once a day for six consecutive days. Animals were sacrificed, bone marrow and blood samples were collected and subjected to series of genotoxicity assay such as micronucleus, chromosome aberration and single cell gel electrophoresis (SCGE) assay respectively. Mutagenicity was determined using tester strains of Salmonella typhimurium (TA 98, TA 100 and TA 102) in the presence and absence of metabolically active microsomal fractions (S9). Further, we estimated the levels of 8-hydroxydeoxyguanosine, lipid per-oxidation and glutathione activity to decipher the potential genotoxic mechanism of BPA. We observed that BPA exposure caused a significant increase in the frequency of micronucleus (MN) in polychromatic erythrocytes (PCEs), structural chromosome aberrations in bone marrow cells and DNA damage in blood lymphocytes. These effects were observed at various doses tested except 2.4 μg compared to vehicle control. We did not observe the mutagenic response in any of the tester strains tested at different concentrations of BPA. We found an increase in the level of 8-hydroxydeoxyguanosine in the plasma and increase in lipid per-oxidation and decrease in glutathione activity in liver of rats respectively which were exposed to BPA. In conclusion, the data obtained clearly documents that BPA is not mutagenic but exhibit genotoxic activity and oxidative stress could be one of the mechanisms leading to genetic toxicity. 相似文献
129.
Priyanka Shah Sumit Kumar Sunita Tiwari Mohammad Imran Siddiqi 《Journal of chemical biology》2012,5(3):91-103
A series of 35 triazolopyrimidine analogues reported as Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors were optimized using quantum mechanics methods, and their binding conformations were studied by docking
and 3D quantitative structure–activity relationship studies. Genetic algorithm-based criteria was adopted for selection of
training and test sets while maintaining structural diversity of training and test sets, which is also very crucial for model
development and validation. Both the comparative molecular field analyses (
q\textLOO2 = 0.841 q_{\text{LOO}}^2 = 0.{841} ,
r\textncv2 = 0.99 r_{\text{ncv}}^2 = 0.{99} ) and comparative molecular similarity indices analyses (
q\textLOO2 = 0.757 q_{\text{LOO}}^2 = 0.{757} ,
r\textncv2 = 0.943 r_{\text{ncv}}^2 = 0.{943} ) show excellent correlation and high predictive power. Furthermore, molecular dynamics simulations were performed to explore
the binding mode of the two of the most active compounds of the series, 10 and 14. Harmonization in the two simulation results validate the analysis and therefore applicability of docking parameters based
on crystallographic conformation of compound 14 bound to receptor molecule. This work provides useful information about the inhibition mechanism of this class of molecules
and will assist in the design of more potent inhibitors of PfDHODH. 相似文献
130.