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101.
Pran Kishore Deb Nizar A. Al-Shari Katharigatta N. Venugopala Melendhran Pillay Pobitra Borah 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):869
The alarming increase in multi- and extensively drug-resistant (MDR and XDR) strains of Mycobacterium tuberculosis (MTB) has triggered the scientific community to search for novel, effective, and safer therapeutics. To this end, a series of 3,5-disubstituted-1,2,4-oxadiazole derivatives (3a–3i) were tested against H37Rv, MDR and XDR strains of MTB. Of which, compound 3a with para-trifluorophenyl substituted oxadiazole showed excellent activity against the susceptible H37Rv and MDR-MTB strain with a MIC values of 8 and 16 µg/ml, respectively.To understand the mechanism of action of these compounds (3a–3i) and identify their putative drug target, molecular docking and dynamics studies were employed against a panel of 20 mycobacterial enzymes reported to be essential for mycobacterial growth and survival. These computational studies revealed polyketide synthase (Pks13) enzyme as the putative target. Moreover, in silico ADMET predictions showed satisfactory properties for these compounds, collectively, making them, particularly compound 3a, promising leads worthy of further optimisation. 相似文献
102.
Konstantinopoulos PA Cannistra SA Fountzilas H Culhane A Pillay K Rueda B Cramer D Seiden M Birrer M Coukos G Zhang L Quackenbush J Spentzos D 《PloS one》2011,6(3):e18202
Background
Public data integration may help overcome challenges in clinical implementation of microarray profiles. We integrated several ovarian cancer datasets to identify a reproducible predictor of survival.Methodology/Principal Findings
Four microarray datasets from different institutions comprising 265 advanced stage tumors were uniformly reprocessed into a single training dataset, also adjusting for inter-laboratory variation (“batch-effect”). Supervised principal component survival analysis was employed to identify prognostic models. Models were independently validated in a 61-patient cohort using a custom array genechip and a publicly available 229-array dataset. Molecular correspondence of high- and low-risk outcome groups between training and validation datasets was demonstrated using Subclass Mapping. Previously established molecular phenotypes in the 2nd validation set were correlated with high and low-risk outcome groups. Functional representational and pathway analysis was used to explore gene networks associated with high and low risk phenotypes. A 19-gene model showed optimal performance in the training set (median OS 31 and 78 months, p<0.01), 1st validation set (median OS 32 months versus not-yet-reached, p = 0.026) and 2nd validation set (median OS 43 versus 61 months, p = 0.013) maintaining independent prognostic power in multivariate analysis. There was strong molecular correspondence of the respective high- and low-risk tumors between training and 1st validation set. Low and high-risk tumors were enriched for favorable and unfavorable molecular subtypes and pathways, previously defined in the public 2nd validation set.Conclusions/Significance
Integration of previously generated cancer microarray datasets may lead to robust and widely applicable survival predictors. These predictors are not simply a compilation of prognostic genes but appear to track true molecular phenotypes of good- and poor-outcome. 相似文献103.
104.
Davita Pillay Julien Izotte Regassa Fikru Philipe Büscher Hermogenes Mucache Luis Neves Alain Boulangé Momar Talla Seck Jérémy Bouyer Grant B. Napier Cyrille Chevtzoff Virginie Coustou Théo Baltz 《PloS one》2013,8(10)
Background
Diagnosis of African animal trypanosomosis is vital to controlling this severe disease which hampers development across 10 million km2 of Africa endemic to tsetse flies. Diagnosis at the point of treatment is currently dependent on parasite detection which is unreliable, and on clinical signs, which are common to several other prevalent bovine diseases.Methodology/Principle Findings
the repeat sequence of the GM6 antigen of Trypanosoma vivax (TvGM6), a flagellar-associated protein, was analysed from several isolates of T. vivax and found to be almost identical despite the fact that T. vivax is known to have high genetic variation. The TvGM6 repeat was recombinantly expressed in E. coli and purified. An indirect ELISA for bovine sera based on this antigen was developed. The TvGM6 indirect ELISA had a sensitivity of 91.4% (95% CI: 91.3 to 91.6) in the period following 10 days post experimental infection with T. vivax, which decreased ten-fold to 9.1% (95% CI: 7.3 to 10.9) one month post treatment. With field sera from cattle infected with T. vivax from two locations in East and West Africa, 91.5% (95% CI: 83.2 to 99.5) sensitivity and 91.3% (95% CI: 78.9 to 93.1) specificity was obtained for the TvGM6 ELISA using the whole trypanosome lysate ELISA as a reference. For heterologous T. congolense field infections, the TvGM6 ELISA had a sensitivity of 85.1% (95% CI: 76.8 to 94.4).Conclusion/Significance
this study is the first to analyse the GM6 antigen of T. vivax and the first to test the GM6 antigen on a large collection of sera from experimentally and naturally infected cattle. This study demonstrates that the TvGM6 is an excellent candidate antigen for the development of a point-of-treatment test for diagnosis of T. vivax, and to a lesser extent T. congolense, African animal trypanosomosis in cattle. 相似文献105.
Canola is second only to soybean as the most important oilseed crop in the world. The global production of canola is forecast to continue to increase and as a result the canola industry will continue to flourish. However, it is threatened by several fungal diseases that affect canola and cost producers hundreds of millions of dollars a year in reduced yield and quality. Blackleg is the most common and devastating disease of canola and is caused by the fungus Leptosphaeria maculans. The fungus can infect any part of the plant at all growth stages and is a serious threat to the canola industry. Novel and more efficient antifungal agents which interfere with fungal growth and development are clearly needed to control this pathogen. This paper reports the establishment of a simple functional assay system for the screening of antifungal proteins against a virulent strain of L. maculans. 相似文献
106.
Govender Algasan Shaik Rehana Pillay Balakrishna 《World journal of microbiology & biotechnology》2011,27(5):1217-1224
1,2-dichloroethane (DCA) is a toxic synthetic haloalkane produced annually in excess of 20 billion tons. Five bacterial isolates
capable of complete mineralization of DCA have recently been isolated from wastewater treatment facilities in South Africa.
Pulsed field gel electrophoresis (PFGE) and random amplification of polymorphic DNA (RAPD) analysis were employed in this
study to identify phylogenetic differences between these closely-related bacteria. Analysis of the 16S rDNA sequences of the
selected isolates revealed similarities to previously characterised isolates of Ancylobacter aquaticus. It has been previously
shown that all isolates follow the same catabolic pathway and possess an identical hydrolytic dehalogenase (DhlA) involved
in the initial carbonchlorine bond cleavage. Analysis of homology matrices deduced from RAPD and restriction profiles, constructed
using the GelCompar software package, revealed that although some of the isolates possessed identical profiles using one primer
or restriction endonuclease, differences were observed when a different primer was used. Furthermore, the results obtained
indicate that the previously characterised isolate A. aquaticus AD25 is significantly different from the isolates used in
this study. PFGE was also able to show that isolates of A. aquaticus do not possess the 200 kb plasmid containing the hydrolytic
dehalogenase gene previously identified in the DCA-degrading bacterium Xanthobacter autotrophicus GJ10. This study has been
able to demonstrate that RAPD and PFGE analysis are suitable molecular tools for the differentiation of closely-related A.
aquaticus isolates and may be routinely used in the differentiation of environmentally important bacteria. 相似文献
107.
Nair SP Peter S Pillay VV Remya UM Krishnaprasad R Rajammal B 《Indian journal of human genetics》2007,13(2):69-72
BACKGROUND:
Circulating fetal cells and cell free DNA in the maternal blood has been shown to help in prenatal diagnosis of genetic disorders without relying on invasive procedures leading to significant risk of pregnancy loss.AIM:
The current study was undertaken to detect the male fetal population using Y STR markers DYS 19, DYS 385 and DYS 392 and also to study the extent of persistence of fetal DNA in the mother following delivery.MATERIALS AND METHODS:
Blinded study was conducted on 50 mothers delivering male and female babies. Cellular and cell free DNA was extracted from maternal and fetal cord blood and amplified for Y STR markers by PCR.RESULTS:
The amplification sensitivity of Y specific STR, DYS19 was 100% (22/22) in the male fetal DNA samples. The incidence of other STRs, i.e., DYS385 and DYS392 were 91% (20/22) each. Analysis of results revealed that thirteen of the twenty six women had detectable male fetal DNA at the time of delivery. However fetal DNA was not detectable twenty four hours after delivery.CONCLUSION:
Preliminary results show that the separation of fetal cell-free DNA in the maternal circulation is a good low-cost approach for the future development of novel strategies to provide non-invasive techniques for early prenatal diagnosis. 相似文献108.
109.
110.
Huw Price Loveleen Bansi Caroline A. Sabin Sanjay Bhagani Andrew Burroughs David Chadwick David Dunn Martin Fisher Janice Main Mark Nelson Deenan Pillay Alison Rodger Chris Taylor Richard Gilson UK Collaborative HIV Cohort Hepatitis Group Steering Committee 《PloS one》2012,7(11)