全文获取类型
收费全文 | 845篇 |
免费 | 48篇 |
出版年
2023年 | 3篇 |
2022年 | 14篇 |
2021年 | 19篇 |
2020年 | 15篇 |
2019年 | 10篇 |
2018年 | 20篇 |
2017年 | 17篇 |
2016年 | 33篇 |
2015年 | 42篇 |
2014年 | 55篇 |
2013年 | 51篇 |
2012年 | 85篇 |
2011年 | 63篇 |
2010年 | 48篇 |
2009年 | 39篇 |
2008年 | 52篇 |
2007年 | 51篇 |
2006年 | 45篇 |
2005年 | 37篇 |
2004年 | 40篇 |
2003年 | 19篇 |
2002年 | 23篇 |
2001年 | 11篇 |
2000年 | 8篇 |
1999年 | 6篇 |
1998年 | 7篇 |
1997年 | 2篇 |
1996年 | 6篇 |
1995年 | 3篇 |
1994年 | 5篇 |
1993年 | 4篇 |
1992年 | 7篇 |
1991年 | 4篇 |
1990年 | 5篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 4篇 |
1979年 | 2篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1971年 | 3篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1964年 | 3篇 |
1963年 | 1篇 |
排序方式: 共有893条查询结果,搜索用时 15 毫秒
1.
Shubhandra Tripathi Akhil Kumar B. Sathish Kumar Arvind S. Negi 《Journal of biomolecular structure & dynamics》2016,34(6):1232-1240
Microtubule stabilizers provide an important mode of treatment via mitotic cell arrest of cancer cells. Recently, we reported two novel neolignans derivatives Cmp10 and Cmp19 showing anticancer activity and working as microtubule stabilizers at micromolar concentrations. In this study, we have explored the binding site, mode of binding, and stabilization by two novel microtubule stabilizers Cmp10 and Cmp19 using in silico molecular docking, molecular dynamics (MD) simulation, and binding free energy calculations. Molecular docking studies were performed to explore the β-tubulin binding site of Cmp10 and Cmp19. Further, MD simulations were used to probe the β-tubulin stabilization mechanism by Cmp10 and Cmp19. Binding affinity was also compared for Cmp10 and Cmp19 using binding free energy calculations. Our docking results revealed that both the compounds bind at Ptxl binding site in β-tubulin. MD simulation studies showed that Cmp10 and Cmp19 binding stabilizes M-loop (Phe272-Val288) residues of β-tubulin and prevent its dynamics, leading to a better packing between α and β subunits from adjacent tubulin dimers. In addition, His229, Ser280 and Gln281, and Arg278, Thr276, and Ser232 were found to be the key amino acid residues forming H-bonds with Cmp10 and Cmp19, respectively. Consequently, binding free energy calculations indicated that Cmp10 (?113.655 kJ/mol) had better binding compared to Cmp19 (?95.216 kJ/mol). This study provides useful insight for better understanding of the binding mechanism of Cmp10 and Cmp19 and will be helpful in designing novel microtubule stabilizers. 相似文献
2.
Scavenging of superoxide radical by ascorbic acid 总被引:1,自引:0,他引:1
Using acetaldehyde and xanthine oxidase as the source of suPeroxide radical, the second order rate constant for the reaction
between ascorbic acid and superoxide radical was estimated to be 8.2 X 107 M-1 s-1. In rats, the average tissue concentration of ascorbic acid was of the order of 10-3 M and that of superoxide dismutase was of the order of 10-6 M. So, taking together both the rate constants and the tissue concentrations, the efficacy of ascorbic acid for scavenging
superoxide radical in animal tissues appears to be better than that of suPeroxide dismutase. The significance of ascorbic
acid as a scavenger of superoxide radical has been discussed from the point of view of the evolution of ascorbic acid synthesizing
capacity of terrestrial vertebrates. 相似文献
3.
The large family of signal transducing proteins known as G proteins are heterotrimers that dissociate into an independent α-subunit and βγ-subunit complex after ligand binding or other stimulation. For Gα, at least 30 distinct sequences representing 10 different classes have been identified. On the other hand, cDNAs for only three Gβ-subunit genes have been isolated so far. All three of the Gβ genes have been chromosomally mapped in the human, but only two in the mouse. Using a human retinal cDNA for the third G protein β-subunit, we have mapped the corresponding gene, termed Gnb-3, to mouse Chromosome 6 with somatic cell hybrids and have positioned it distal to but near the marker Raf-1 by analysis of the progeny of three genetic crosses. 相似文献
4.
Summary In the qualitative short-day plant Impatiens balsamina, gibberellic acid (GA3) not only promoted the formation of floral buds in response to suboptimal photoinductive conditions and reduced the number of SD cycles that are required for their development into flowers, but also caused initiation of floral buds under non-inductive photoperiods. In plants treated with repeated applications of GA3, the floral buds developed into flowers irrespective of whether the apex was left intact or was removed. In those that received a single application of GA3 the floral buds developed into flowers only in decapitated plants. 相似文献
5.
6.
R. Kapila M. S. Negi P. This M. Delseny P. S. Srivastava M. Lakshmikumaran 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1996,93(7):1123-1129
The 459-bp HindIII (pBN-4) and the 1732-bp Eco RI (pBNE8) fragments from the Brassica nigra genome were cloned and shown to be members of a dispersed repeat family. Of the three major diploid Brassica species, the repeat pBN-4 was found to be highly specific for the B. nigra genome. The family also hybridized to Sinapis arvensis showing that B. nigra had a closer relationship with the S. arvensis genome than with B. oleracea or B. campestris. The clone pBNE8 showed homology to a number of tRNA species indicating that this family of repeats may have originated from a tRNA sequence. The species-specific 459-bp repeat pBN-4 was localized on the B. nigra chromosomes using monosomic addition lines. In addition to the localization of pBN-4, the chromosomal distribution of two other species-specific repeats, pBN34 and pBNBH35 (reported earlier), was studied. The dispersed repeats pBN-4 and pBNBH35 were found to be present on all of the chromosomes, whereas the tandem repeat pBN34 was localized on two chromosomes. 相似文献
7.
The responses of seedlings of three fast growing tree species,Eucalyptus hybrid(E. camaldulensis × E. teriticornis), Casuarina equisetifolia andMelia azedarach, to different levels of soil moisture in controlled glasshouse conditions were compared. The survival percentage, height of plants, number of leaves per plant, number of branches, fresh mass and dry mass of roots, stems, branches and leaves decreased in the three species with increasing water stress. Stomatal frequency and length of stomata inEucalyptus andMelia also decreased with increasing water stress. However, no significant difference was obtained in the width of stomata and the ratio of number of open stomata to total number of stomata per unit area. The leaf thickness decreased, but the thickness of palisade parenchyma increased with increasing water stress inEucalyptus hybrid andCasuarina. Leaf thickness ofMelia did not show any significant variation due to water stress. 相似文献
8.
Keratinolytic proteinase produced by Candida albicans 总被引:11,自引:0,他引:11
Candida albicans was cultivated in various media that contained human stratum corneum, human scalp hair or keratin powder (cow's hoof) as a nitrogen source. Production of a keratinolytic proteinase (KPase) was observed when C. albicans was incubated in the medium containing stratum corneum. However, there was no production of a KPase that could digest human stratum corneum in the medium containing hair or keratin powder. alpha-fibrous protein extracted from human stratum corneum was digested by the KPase. The pH optimum of the enzyme was 4.0 and enzyme activity was inhibited by pepstatin A and chymostatin. The KPase, a kind of carboxyl proteinase, may be important for C. albicans to enable it to play a pathogenic role in vivo. 相似文献
9.
Alterations of Phospholipid Metabolism in Rat Cerebral Cortex Mince Induced by Cationic Amphiphilic Drugs 总被引:3,自引:3,他引:0
Abstract Cationic amphiphilic drugs (CADs) of varied clinical use were screened to determine their capacity to alter the pattern of labeling with 32 Pj of cerebral cortex mince phospholipids. The altered phospholipid labeling patterns were qualitatively similar, the prominent features being reduced incorporation into phosphatidylcholine and increased incorporation into phosphatidic acid. Relative potencies were: (±)-propranolol > chlorpromazine = 4,4'-bis(diethylaminoethoxy) α,β -diethyldiphenylethane > desipramine > di-bucaine > pimozide > oxymetazoline = fenfluramine = haloperidol = chloroquine > amphetamine = no drug added. Propranolol was used to study the action of CADs further. Its effect was time- and dose-dependent, but in contrast with pineal gland, no label appeared in phosphatidyl-CMP (CDP-diacylglycerol), nor did dialysis of the mince to reduce diffusible substrates or exogenous addition of substrates cause appearance of liponucleotide. Thus lack of diffusible precursors is not responsible for CAD effects in vitro. Pulse-chase experiments with 32 P1 and [2-3 H]glycerol suggested that inhibition of phosphatidate phosphohydrolase may be partly responsible for the observed alterations in phospholipid labeling in the presence of CADs. 相似文献
10.
Saravanan Munisankar Anuradha Rajamanickam Suganthi Balasubramanian Satishwaran Muthusamy Chandra Kumar Dolla Pradeep Aravindan Menon Ponnuraja Chinnayan Christopher Whalen Paschaline Gumne Inderdeep Kaur Varma Nadimpalli Akshay Deverakonda Zhenhao Chen John David Otto Tesfalidet Habitegiyorgis Harish Kandaswamy Thomas B. Nutman Subash Babu 《PLoS neglected tropical diseases》2022,16(7)
BackgroundThe prevalence of Strongyloides stercoralis infection is estimated to be 30–100 million worldwide, although this an underestimate. Most cases remain undiagnosed due to the asymptomatic nature of the infection. We wanted to estimate the seroprevalence of S. stercoralis infection in a South Indian adult population.MethodsTo this end, we performed community-based screening of 2351 individuals (aged 18–65) in Kanchipuram District of Tamil Nadu between 2013 and 2020. Serological testing for S. stercoralis was performed using the NIE ELISA.ResultsOur data shows a seroprevalence of 33% (768/2351) for S. stercoralis infection which had a higher prevalence among males 36% (386/1069) than among females 29.8% (382/1282). Adults aged ≥55 (aOR = 1.65, 95% CI: 1.25–2.18) showed higher adjusted odds of association compared with other age groups. Eosinophil levels (39%) (aOR = 1.43, 95% CI: 1.19–1.74) and hemoglobin levels (24%) (aOR = 1.25, 95% CI: 1.11–1.53) were significantly associated with S. stercoralis infection. In contrast, low BMI (aOR = 1.15, 95% CI: 0.82–1.61) or the presence of diabetes mellitus (OR = 1.18, 95% CI: 0.83–1.69) was not associated with S. stercoralis seropositivity.ConclusionsOur study provides evidence for a very high baseline prevalence of S. stercoralis infection in South Indian communities and this information could provide realistic and concrete planning of control measures. 相似文献