全文获取类型
收费全文 | 112篇 |
免费 | 13篇 |
出版年
2023年 | 1篇 |
2022年 | 2篇 |
2021年 | 3篇 |
2020年 | 3篇 |
2019年 | 1篇 |
2018年 | 6篇 |
2017年 | 4篇 |
2016年 | 10篇 |
2015年 | 7篇 |
2014年 | 8篇 |
2013年 | 6篇 |
2012年 | 10篇 |
2011年 | 10篇 |
2010年 | 4篇 |
2009年 | 4篇 |
2008年 | 2篇 |
2007年 | 7篇 |
2006年 | 1篇 |
2005年 | 5篇 |
2004年 | 8篇 |
2003年 | 9篇 |
2002年 | 3篇 |
2001年 | 1篇 |
1999年 | 2篇 |
1998年 | 1篇 |
1997年 | 2篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1987年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
排序方式: 共有125条查询结果,搜索用时 31 毫秒
21.
D. R. Gillespie D. J. M. Quiring R. G. Foottit S. P. Foster S. Acheampong 《Journal of Applied Entomology》2009,133(7):505-511
Variation in vulnerability to natural enemies, reproductive rate and insecticide resistance among phenotypes of Myzus persicae (Sulzer) has been shown to have the potential to disrupt biological control and IPM of this species, and movement of particularly troublesome phenotypes in international horticultural trade could be cause for concern. Three important components of fitness, vulnerability to parasitoids, reproduction and insecticide resistance were determined in three clones of M. persicae originating from prevalent phenotype populations on pepper crops in greenhouses in British Columbia, Canada. One of these phenotypes appeared to be consistently involved in outbreaks in commercial operations. These clones were also characterized for their DNA microsatellite genotype and compared with genotypes of M. persicae from Europe. The clone involved in outbreaks in commercial greenhouses showed reduced vulnerability to parasitoids, and a higher reproductive rate compared to the other two clones suggesting that these traits may have been involved in outbreaks. As in M. persicae European clones, a higher reproductive rate was correlated with a lack of esterase‐based resistance (primarily to organophosphates and, to some extent, to carbamates and pyrethroids). However, microsatellite analysis demonstrated that the three clones investigated in British Columbia had unique genotypes, and therefore there was no evidence for their movement in international trade. 相似文献
22.
Kwame Shanaube Charalambos Sismanidis Helen Ayles Nulda Beyers Ab Schaap Katherine-Anne Lawrence Annie Barker Peter Godfrey-Faussett 《PloS one》2009,4(11)
Background
The annual risk of tuberculous infection (ARTI) is a key epidemiological indicator of the extent of transmission in a community. Several methods have been suggested to estimate the prevalence of tuberculous infection using tuberculin skin test data. This paper explores the implications of using different methods to estimate prevalence of infection and ARTI. The effect of BCG vaccination on these estimates is also investigated.Methodology/Principal Findings
Tuberculin surveys among school children in 16 communities in Zambia and 8 in South Africa (SA) were performed in 2005, as part of baseline data collection and for randomisation purposes of the ZAMSTAR study. Infection prevalence and ARTI estimates were calculated using five methods: different cut-offs with or without adjustments for sensitivity, the mirror method, and mixture analysis. A total of 49,835 children were registered for the surveys, of which 25,048 (50%) had skin tests done and 22,563 (90%) of those tested were read. Infection prevalence was higher in the combined SA than Zambian communities. The mirror method resulted in the least difference of 7.8%, whereas that estimated by the cut-off methods varied from 12.2% to 17.3%. The ARTI in the Zambian and SA communities was between 0.8% and 2.8% and 2.5% and 4.2% respectively, depending on the method used. In the SA communities, the ARTI was higher among the younger children. BCG vaccination had little effect on these estimates.Conclusions/Significance
ARTI estimates are dependent on the calculation method used. All methods agreed that there were substantial differences in infection prevalence across the communities, with higher rates in SA. Although TB notification rates have increased over the past decades, the difference in cumulative exposure between younger and older children is less dramatic and a rise in risk of infection in parallel with the estimated incidence of active tuberculosis cannot be excluded. 相似文献23.
Background
Ovarian cancer is the most lethal gynecological malignancy, and the ovarian clear cell carcinoma subtype (OCCA) demonstrates a particularly poor response to standard treatment. Improvements in ovarian cancer outcomes, especially for OCCA, could be expected from a clearer understanding of the molecular pathology that might guide strategies for earlier diagnosis and more effective treatment.Methodology/Principal Findings
Cell-SELEX technology was employed to develop new molecular probes for ovarian cancer cell surface markers. A total of thirteen aptamers with Kd''s to ovarian cancer cells in the pico- to nanomolar range were obtained. Preliminary investigation of the targets of these aptamers and their binding characteristics was also performed.Conclusions/Significance
We have selected a series of aptamers that bind to different types of ovarian cancer, but not cervical cancer. Though binding to other cancer cell lines was observed, these aptamers could lead to identification of biomarkers that are related to cancer. 相似文献24.
DNA aptamers as molecular probes for colorectal cancer study 总被引:1,自引:0,他引:1
Background
Understanding the molecular features of specific tumors can increase our knowledge about the mechanism(s) underlying disease development and progression. This is particularly significant for colorectal cancer, which is a heterogeneous complex of diseases developed in a sequential manner through a multistep carcinogenic process. As such, it is likely that tumors with similar characteristics might originate in the same manner and have a similar molecular behavior. Therefore, specific mapping of the molecular features can be potentially useful for both tumor classification and the development of appropriate therapeutic regimens. However, this can only be accomplished by developing high-affinity molecular probes with the ability to recognize specific markers associated with different tumors. Aptamers can most easily meet this challenge based on their target diversity, flexible manipulation and ease of development.Methodology and Results
Using a method known as cell-based Systematic Evolution of Ligands by Exponential enrichment (cell-SELEX) and colorectal cancer cultured cell lines DLD-1 and HCT 116, we selected a panel of target-specific aptamers. Binding studies by flow cytometry and confocal microscopy showed that these aptamers have high affinity and selectivity. Our data further show that these aptamers neither recognize normal colon cells (cultured and fresh), nor do they recognize most other cancer cell lines tested.Conclusion/Significance
The selected aptamers can identify specific biomarkers associated with colorectal cancers. We believe that these probes could be further developed for early disease detection, as well as prognostic markers, of colorectal cancers. 相似文献25.
Jeffery S Crosby A Plange-Rhule J Amoah-Danquah J Acheampong JW Eastwood JB Malik AK 《Genetic testing》1999,3(4):375-377
Mutations in the HFE gene on chromosome 6 are believed to cause the iron overload disorder hemochromatosis, the most common single gene disorder in northern Europeans. Two mutations have been described previously: C282Y, with an allele frequency of between 3% and 10% in the caucasian population, and H63D, which has an allele frequency of 16%. Published data shows that C282Y appears to be causative in the homozygous state, while the frequency of H63D/C282Y compound heterozygotes is much greater than expected in patient groups. There also appears to be a slightly elevated risk for H63D homozygotes. Hemochromatosis has been thought to be primarily a caucasian disorder. We have studied 97 healthy, black Ghanaian subjects, whose parents and grandparents were also African, to find the frequency of the two mutations. C282Y was absent, while H63D occurred in 2 individuals. These differences are significant at the 0.05 and 0.001 levels, respectively. The prevalence of H63D homozygotes in this population at 1 in 10,000 is clearly of no use in studying the effect of this genotype on phenotype. However, this study suggests an absence of the C282Y mutation in African populations, and the possibility that other populations might provide different genotypes and hence an analysis of H63D risk. A possible heterozygote advantage for the mutation is discussed. 相似文献
26.
Daniel J. Metcalfe Aida Cuni Sanchez P. Michael Curran Jens Å. R. Haga Hamza Khalid Kija Elizabeth J. Kleynhans Mirjam Kopp Sinagabe U. Korogone Ireene R. Madindou Albert Minlend Felix Ndagijimana Thenjiwe C. Ndlovu Ernest Nti Acheampong Clive Nuttman Karin H. Olsson Dimby Rahrinjanahary Hanta J. Razafimanahaka Josia Razafindramanana Zuzanna Rykowska Ravi Sachdev Laura Simpson Rosie Trevelyan 《African Journal of Ecology》2007,45(4):464-468
27.
Argyris EG Acheampong E Nunnari G Mukhtar M Williams KJ Pomerantz RJ 《Journal of virology》2003,77(22):12140-12151
Several studies have reported a crucial role for cholesterol-enriched membrane lipid rafts and cell-associated heparan sulfate proteoglycans (HSPGs), a class of molecules that can localize in lipid rafts, in the entry of human immunodeficiency virus type 1 (HIV-1) into permissive cells. For the present study, we examined the role of these cell surface moieties in HIV-1 entry into primary human brain microvascular endothelial cells (BMVECs), which represent an important HIV-1 central nervous system-based cell reservoir and a portal for neuroinvasion. Cellular cholesterol was depleted by exposure to beta-cyclodextrins and 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A reductase inhibitors (statins), the loss of cholesterol was quantitated, and disruption of membrane rafts was verified by immunofluorescence. Nevertheless, these treatments did not affect binding of several strains of HIV-1 virions to BMVECs at 4 degrees C or their infectivities at 37 degrees C. In contrast, we confirmed that cholesterol depletion and raft disruption strongly inhibited HIV-1 binding and infection of Jurkat T cells. Enzymatic digestion of cell-associated HSPGs on human BMVECs dramatically inhibited HIV-1 infection, and our data from quantitative HIV-1 DNA PCR analysis strongly suggest that cell-associated chondroitin sulfate proteoglycans greatly facilitate infective entry of HIV-1 into human BMVECs. These findings, in combination with our earlier work showing that human BMVECs lack CD4, indicate that the molecular mechanisms for HIV-1 entry into BMVECs are fundamentally different from that of viral entry into T cells, in which lipid rafts, CD4, and probably HSPGs play important roles. 相似文献
28.
29.
beta-Synuclein reduces proteasomal inhibition by alpha-synuclein but not gamma-synuclein 总被引:4,自引:0,他引:4
Snyder H Mensah K Hsu C Hashimoto M Surgucheva IG Festoff B Surguchov A Masliah E Matouschek A Wolozin B 《The Journal of biological chemistry》2005,280(9):7562-7569
The accumulation of aggregated alpha-synuclein is thought to contribute to the pathogenesis of Parkinson's disease. Recent studies indicate that aggregated alpha-synuclein binds to S6', a component of the 19 S subunit in the 26 S proteasome and inhibits 26 S proteasomal degradation, both ubiquitin-independent and ubiquitin-dependent. The IC(50) of aggregated alpha-synuclein for inhibition of the 26 S ubiquitin-independent proteasomal activity is approximately 1 nm. alpha-Synuclein has two close homologues, termed beta-synuclein and gamma-synuclein. In the present study we compared the effects of the three synuclein homologues on proteasomal activity. The proteasome exists as a 26 S and a 20 S species, with the 26 S proteasome containing the 20 S core and 19 S cap. Monomeric alpha- and beta-synucleins inhibited the 20 S and 26 S proteasomal activities only weakly, but monomeric gamma-synuclein strongly inhibited ubiquitin-independent proteolysis. The IC(50) of monomeric gamma-synuclein for the 20 S proteolysis was 400 nm. In monomeric form, none of the three synuclein proteins inhibited 26 S ubiquitin-dependent proteasomal activity. Although beta-synuclein had no direct effect on proteasomal activity, co-incubating monomeric beta-synuclein with aggregated alpha-synuclein antagonized the inhibition of the 26 S ubiquitin-independent proteasome by aggregated alpha-synuclein when added before the aggregated alpha-synuclein. Co-incubating beta-synuclein with gamma-synuclein had no effect on the inhibition of the 20 S proteasome by monomeric gamma-synuclein. Immunoprecipitation and pull-down experiments suggested that antagonism by beta-synuclein resulted from binding to alpha-synuclein rather than binding to S6'. Pull-down experiments demonstrated that recombinant monomeric beta-synuclein does not interact with the proteasomal subunit S6', unlike alpha-synuclein, but beta-synuclein does bind alpha-synuclein and competes with S6' for binding to alpha-synuclein. Based on these data, we hypothesize that the alpha- and gamma-synucleins regulate proteasomal function and that beta-synuclein acts as a negative regulator of alpha-synuclein. 相似文献
30.
We report the expression of 3 well-characterized adult Schistosoma mansoni glycan antigens among molluscan stages of the parasite. These antigens are LacdiNAc (LDN; GalNAcbeta1-4GlcNAc-R), fucosylated LacdiNAc (LDNF; GalNAc[Fucal-3]beta1-4GlcNAc-R), and Lewis x (Le(x); Gal[Fucalpha1-3]beta1-4GlcNAc-R). The presence of the glycans was determined by both immunoblot and immunohistological methods using monoclonal antibodies that specifically recognize each glycan epitope. Immunoblot analyses reveal that LDN and LDNF epitopes are expressed on many different glycoproteins, including eggs, mother sporocysts, daughter sporocysts, and cercariae, although LDN expression among daughter sporocysts is greatly reduced. LDN and LDNF epitopes are localized on the tegument and in the intrasporocyst cell masses of both in vitro-derived and in vivo-derived mother sporocysts and in the daughter sporocysts derived on day 16 after infection. Unexpectedly, high levels of LDN and LDNF glycans were detected in the infected, but not in the uninfected, snail hemolymph, suggesting that the infecting larvae secrete LDN and LDNF glycoconjugates into the snail hosts. In contrast, the expression of Le(x) antigen among the molluscan stages is highly restricted. Le(x) is present on a few high-molecular weight glycoproteins in eggs and cercariae but is undetectable in mother and daughter sporocysts. Taken together with our earlier studies on vertebrate stages of S. mansoni, these results show that LDN and LDNF glycans are conserved during schistosome development. The study further extends the evidence that Le(x) is a developmentally regulated antigen in schistosomes. 相似文献