全文获取类型
收费全文 | 270篇 |
免费 | 33篇 |
国内免费 | 3篇 |
出版年
2022年 | 4篇 |
2021年 | 5篇 |
2020年 | 2篇 |
2019年 | 6篇 |
2018年 | 5篇 |
2017年 | 4篇 |
2016年 | 10篇 |
2015年 | 10篇 |
2014年 | 16篇 |
2013年 | 14篇 |
2012年 | 22篇 |
2011年 | 21篇 |
2010年 | 12篇 |
2009年 | 19篇 |
2008年 | 9篇 |
2007年 | 10篇 |
2006年 | 16篇 |
2005年 | 14篇 |
2004年 | 15篇 |
2003年 | 10篇 |
2002年 | 7篇 |
2001年 | 11篇 |
2000年 | 8篇 |
1999年 | 4篇 |
1998年 | 5篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 5篇 |
1992年 | 4篇 |
1991年 | 5篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1988年 | 4篇 |
1987年 | 5篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1976年 | 1篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1969年 | 1篇 |
排序方式: 共有306条查询结果,搜索用时 265 毫秒
31.
Jonathan M. Carlson Chanson J. Brumme Eric Martin Jennifer Listgarten Mark A. Brockman Anh Q. Le Celia K. S. Chui Laura A. Cotton David J. H. F. Knapp Sharon A. Riddler Richard Haubrich George Nelson Nico Pfeifer Charles E. DeZiel David Heckerman Richard Apps Mary Carrington Simon Mallal P. Richard Harrigan Mina John Zabrina L. Brumme the International HIV Adaptation Collaborative 《Journal of virology》2012,86(24):13202-13216
HLA class I-associated polymorphisms identified at the population level mark viral sites under immune pressure by individual HLA alleles. As such, analysis of their distribution, frequency, location, statistical strength, sequence conservation, and other properties offers a unique perspective from which to identify correlates of protective cellular immunity. We analyzed HLA-associated HIV-1 subtype B polymorphisms in 1,888 treatment-naïve, chronically infected individuals using phylogenetically informed methods and identified characteristics of HLA-associated immune pressures that differentiate protective and nonprotective alleles. Over 2,100 HLA-associated HIV-1 polymorphisms were identified, approximately one-third of which occurred inside or within 3 residues of an optimally defined cytotoxic T-lymphocyte (CTL) epitope. Differential CTL escape patterns between closely related HLA alleles were common and increased with greater evolutionary distance between allele group members. Among 9-mer epitopes, mutations at HLA-specific anchor residues represented the most frequently detected escape type: these occurred nearly 2-fold more frequently than expected by chance and were computationally predicted to reduce peptide-HLA binding nearly 10-fold on average. Characteristics associated with protective HLA alleles (defined using hazard ratios for progression to AIDS from natural history cohorts) included the potential to mount broad immune selection pressures across all HIV-1 proteins except Nef, the tendency to drive multisite and/or anchor residue escape mutations within known CTL epitopes, and the ability to strongly select mutations in conserved regions within HIV''s structural and functional proteins. Thus, the factors defining protective cellular immune responses may be more complex than simply targeting conserved viral regions. The results provide new information to guide vaccine design and immunogenicity studies. 相似文献
32.
33.
Yiu-Loon Chui Arthur Ka-Keung Ching Fung-Ping Yip Anthony Edward James John Yuek-Hon Chan 《Biochemical and biophysical research communications》2010,391(3):1522-1525
BRE, also known as TNFRSF1A modulator and BRCC45, is an evolutionarily highly conserved protein. It is a death receptor-associated protein in cytoplasm and a component of BRCA1/2-containing DNA repair complex in nucleus. BRE was found to have anti-apoptotic activity. Over-expression of BRE by transfection promoted survival of cell lines against apoptotic induction; whereas depletion of the protein by siRNA resulted in the opposite. In vivo anti-apoptotic activity of BRE was demonstrated by significant attenuation of Fas-induced acute fulminant hepatitis in transgenic mice expressing the human protein specifically in the liver. BRE was also implicated in tumor promotion by the accelerated tumor growth of Lewis Lung carcinoma transfected with human BRE; and by high expression of BRE specifically in the tumoral regions of human hepatocellular carcinoma (HCC). The present study was to test directly if transgenic expression of BRE in livers could promote HCC development in neonatal diethylnitrosamine model. By 8 months after tumor induction, the maximal sizes of tumor nodules of transgenic mice were significantly larger than those of the non-transgenic controls, although the numbers of tumor nodules between the two groups did not significantly differ. Importantly, as in human HCC, the mouse endogenous BRE level was up-regulated in mouse HCC nodules. These results show that BRE over-expression can indeed promote growth, though not initiation, of liver tumors. Furthermore, the common occurrence of BRE over-expression in human and mouse HCC suggests that up-regulation of BRE is functionally important in liver tumor development. 相似文献
34.
Chui Wan Cheung Markus Berger Matthias Finkbeiner 《The International Journal of Life Cycle Assessment》2018,23(1):82-94
Purpose
The current focus of environmental legislation for energy-using products is an efficient energy consumption in the use stage. However, the production and waste treatment of electronic products are also related to environmental impacts in terms of declining metal resources and growing waste streams. This paper investigates the environmental impacts of life time extension versus energy efficiency for the product group video projector using life cycle assessment (LCA).Methods
The product under study was an average video projector based on three LCD projectors. The studied systems included two possibilities after a regular first usage period: reconditioning for a second use or replacement by a primary successor with an energy efficiency increase of 5 and 10%. All impacts addressed were accounted using the ReCiPe 2008 method. The impact contribution of projector components was identified at midpoint and endpoint levels, while life cycle impacts were calculated with a focus on three impact categories. Furthermore, the amortization period of production emissions was quantified.Results and discussion
LCA results showed that the use stage dominates life cycle impacts of the global warming potential and primary energy demand. For the metal depletion potential, the production stage accounts for most of the total life cycle load. The highest shares in production emissions were identified for electronic components, namely printed wired boards and integrated circuits. Reconditioning and reuse of a secondary projector resulted in minor environmental impacts compared to the replacement and use of a primary projector with an energy efficiency increase of 5%. The saving potential of the primary energy demand is higher only in the case of a 10% more efficient device as compared to the secondary projector.Conclusions
The study concluded that production emissions and their amortization period are relevant factors offsetting any environmentally beneficial measures applied during the use phase. The study suggests that life time extension of video projectors can provide higher environmental improvement potentials, while energy efficiency increase during usage is less beneficial, given that major improvements in energy efficiency do not occur. Recommendations are valid for this particular case study. The study suggests that the current focus of mandatory product requirements for energy-using products on energy efficiency increase should be extended to measures of life time extension in order to serve the intent of an integrated product policy.35.
36.
37.
Chung-Hin Chui Raymond Siu-Ming Wong Roberto Gambari Gregory Yin-Ming Cheng Marcus Chun-Wah Yuen Kit-Wah Chan See-Wai Tong Fung-Yi Lau Paul Bo-San Lai Kim-Hung Lam Cheuk-Lam Ho Chi-Wai Kan Kelvin Sze-Yin Leung Wai-Yeung Wong 《Bioorganic & medicinal chemistry》2009,17(23):7872-7877
A list of diethynylfluorenes and their gold(I) derivatives have been studied for their antitumor activity as a function of their structure–activity relationships. End-capping the fluoren-9-one unit with gold(I) moieties could significantly strengthen the cytotoxic activity in vitro on three human cancer cell lines with induction of reactive oxygen species generation on Hep3B hepatocellular carcinoma cells and exhibit attractive antitumor activity from in vivo nude mice Hep3B xenograft model with limited adverse effects on vital organs including liver and kidney. 相似文献
38.
Michael CW Chan Renee WY Chan Wendy CL Yu Carol CC Ho WH Chui CK Lo Kit M Yuen Yi Guan John M Nicholls JS Malik Peiris 《Respiratory research》2009,10(1):102
Background
Highly pathogenic avian influenza (HPAI) H5N1 virus is entrenched in poultry in Asia and Africa and continues to infect humans zoonotically causing acute respiratory disease syndrome and death. There is evidence that the virus may sometimes spread beyond respiratory tract to cause disseminated infection. The primary target cell for HPAI H5N1 virus in human lung is the alveolar epithelial cell. Alveolar epithelium and its adjacent lung microvascular endothelium form host barriers to the initiation of infection and dissemination of influenza H5N1 infection in humans. These are polarized cells and the polarity of influenza virus entry and egress as well as the secretion of cytokines and chemokines from the virus infected cells are likely to be central to the pathogenesis of human H5N1 disease.Aim
To study influenza A (H5N1) virus replication and host innate immune responses in polarized primary human alveolar epithelial cells and lung microvascular endothelial cells and its relevance to the pathogenesis of human H5N1 disease.Methods
We use an in vitro model of polarized primary human alveolar epithelial cells and lung microvascular endothelial cells grown in transwell culture inserts to compare infection with influenza A subtype H1N1 and H5N1 viruses via the apical or basolateral surfaces.Results
We demonstrate that both influenza H1N1 and H5N1 viruses efficiently infect alveolar epithelial cells from both apical and basolateral surface of the epithelium but release of newly formed virus is mainly from the apical side of the epithelium. In contrast, influenza H5N1 virus, but not H1N1 virus, efficiently infected polarized microvascular endothelial cells from both apical and basolateral aspects. This provides a mechanistic explanation for how H5N1 virus may infect the lung from systemic circulation. Epidemiological evidence has implicated ingestion of virus-contaminated foods as the source of infection in some instances and our data suggests that viremia, secondary to, for example, gastro-intestinal infection, can potentially lead to infection of the lung. HPAI H5N1 virus was a more potent inducer of cytokines (e.g. IP-10, RANTES, IL-6) in comparison to H1N1 virus in alveolar epithelial cells, and these virus-induced chemokines were secreted onto both the apical and basolateral aspects of the polarized alveolar epithelium.Conclusion
The predilection of viruses for different routes of entry and egress from the infected cell is important in understanding the pathogenesis of influenza H5N1 infection and may help unravel the pathogenesis of human H5N1 disease. 相似文献39.
40.
Xing GUO Mark P. SIMMONS Paul Pui‐Hay BUT Pang‐Chui SHAW Rui‐Jiang WANG 《植物分类学报:英文版》2011,49(3):203-212
The potential application of DNA barcodes of plastid (matK, trnH–psbA, petD, and rbcL) and nuclear (internal transcribed spacer (ITS) of rDNA) DNA regions was investigated for 25 Hedyotis taxa. The ITS showed the best species discrimination by resolving 23 of the species as exclusive lineages with no shared alleles between any of the 24 distinct species (H. assimilis and H. mellii are not supported as distinct species based on our molecular and morphological data). Conversely, rbcL performed the worst and only resolved 10 of the species as exclusive lineages, and 10 species with shared alleles. Using ITS has the advantage of high PCR amplification success and it provides good intra- and interspecific variation distribution patterns. The most powerful plastid markers were petD and trnH–psbA, but we could amplify and sequence trnH–psbA for only 83% of the accessions sampled. Combination of ITS and petD performed extremely well, with all 24 of the distinct species resolved as exclusive lineages and no shared alleles between any of the distinct species. We therefore recommend ITS, or a combination of ITS and petD, as the standard DNA barcode in Hedyotis, but acknowledge that there are no shared alleles between distinct species for matK and rbcL combined. 相似文献