全文获取类型
收费全文 | 184篇 |
免费 | 18篇 |
出版年
2023年 | 1篇 |
2022年 | 5篇 |
2021年 | 4篇 |
2020年 | 1篇 |
2019年 | 1篇 |
2018年 | 4篇 |
2017年 | 4篇 |
2016年 | 10篇 |
2015年 | 8篇 |
2014年 | 5篇 |
2013年 | 15篇 |
2012年 | 19篇 |
2011年 | 17篇 |
2010年 | 12篇 |
2009年 | 11篇 |
2008年 | 14篇 |
2007年 | 4篇 |
2006年 | 7篇 |
2005年 | 5篇 |
2004年 | 13篇 |
2003年 | 8篇 |
2002年 | 12篇 |
2001年 | 2篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 1篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1983年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1977年 | 1篇 |
排序方式: 共有202条查询结果,搜索用时 15 毫秒
121.
122.
Giovanna Clavarino Nuno Cl��udio Th��r��se Couderc Alexandre Dalet Delphine Judith Voahirana Camosseto Enrico K. Schmidt Till Wenger Marc Lecuit Evelina Gatti Philippe Pierre 《PLoS pathogens》2012,8(5)
Nucleic acid sensing by cells is a key feature of antiviral responses, which generally result in type-I Interferon production and tissue protection. However, detection of double-stranded RNAs in virus-infected cells promotes two concomitant and apparently conflicting events. The dsRNA-dependent protein kinase (PKR) phosphorylates translation initiation factor 2-alpha (eIF2α) and inhibits protein synthesis, whereas cytosolic DExD/H box RNA helicases induce expression of type I-IFN and other cytokines. We demonstrate that the phosphatase-1 cofactor, growth arrest and DNA damage-inducible protein 34 (GADD34/Ppp1r15a), an important component of the unfolded protein response (UPR), is absolutely required for type I-IFN and IL-6 production by mouse embryonic fibroblasts (MEFs) in response to dsRNA. GADD34 expression in MEFs is dependent on PKR activation, linking cytosolic microbial sensing with the ATF4 branch of the UPR. The importance of this link for anti-viral immunity is underlined by the extreme susceptibility of GADD34-deficient fibroblasts and neonate mice to Chikungunya virus infection. 相似文献
123.
Ribosomal protein mRNAs are translationally-regulated during human dendritic cells activation by LPS
Maurizio Ceppi Giovanna Clavarino Evelina Gatti Enrico K Schmidt Aude de Gassart Derek Blankenship Gerald Ogola Jacques Banchereau Damien Chaussabel Philippe Pierre 《Immunome research》2009,5(1):1-12
Background
Using a combined in silico approach, we investigated the glycosylation of T cell epitopes and autoantigens. The present systems biology analysis was made possible by currently available databases (representing full proteomes, known human T cell epitopes and autoantigens) as well as glycosylation prediction tools.Results
We analyzed the probable glycosylation of human T cell epitope sequences extracted from the ImmuneEpitope Database. Our analysis suggests that in contrast to full length SwissProt entries, only a minimal portion of experimentally verified T cell epitopes is potentially N- or O-glycosylated (2.26% and 1.22%, respectively). Bayesian analysis of entries extracted from the Autoantigen Database suggests a correlation between N-glycosylation and autoantigenicity. The analysis of random generated sequences shows that glycosylation probability is also affected by peptide length. Our data suggest that the lack of peptide glycosylation, a feature that probably favors effective recognition by T cells, might have resulted in a selective advantage for short peptides to become T cell epitopes. The length of T cell epitopes is at the intersection of curves determining specificity and glycosylation probability. Thus, the range of length of naturally occurring T cell epitopes may ensure the maximum specificity with the minimal glycosylation probability.Conclusion
The findings of this bioinformatical approach shed light on fundamental factors that might have shaped adaptive immunity during evolution. Our data suggest that amino acid sequence-based hypo/non-glycosylation of certain segments of proteins might be substantial for determining T cell immunity/autoimmunity. 相似文献124.
Evelina L. Zdorovenko Olga A. Valueva Vladimir V. Shubchinskiy Yuriy A. Knirel 《Carbohydrate research》2010,345(12):1812-149
The O-polysaccharide of Pragia fontium 97U116 was obtained by mild acid degradation of the lipopolysaccharide and studied by sugar analysis along with 1D and 2D 1H and 13C NMR spectroscopy. The following structure of the pentasaccharide-repeating unit was established: →2)-α-d-Galf-(1→3)-α-l-Rhap2AcI-(1→4)-α-d-GlcpNAcI-(1→2)-α-l-RhapII-(1→3)-β-d-GlcpNAcII-(1→ 相似文献
125.
Elke S Bergmann-Leitner Ryan M. Mease Patricia De La Vega Tatyana Savranskaya Mark Polhemus Christian Ockenhouse Evelina Angov 《PloS one》2010,5(8)
Background
The Plasmodium protein Cell-traversal protein for ookinetes and sporozoites (CelTOS) plays an important role in cell traversal of host cells in both, mosquito and vertebrates, and is required for successful malaria infections. CelTOS is highly conserved among the Plasmodium species, suggesting an important functional role across all species. Therefore, targeting the immune response to this highly conserved protein and thus potentially interfering with its biological function may result in protection against infection even by heterologous species of Plasmodium.Methodology/Principal Findings
To test this hypothesis, we developed a recombinant codon-harmonized P. falciparum CelTOS protein that can be produced to high yields in the E. coli expression system. Inbred Balb/c and outbred CD-1 mice were immunized with various doses of the recombinant protein adjuvanted with Montanide ISA 720 and characterized using in vitro and in vivo analyses.Conclusions/Significance
Immunization with PfCelTOS resulted in potent humoral and cellular immune responses and most importantly induced sterile protection against a heterologous challenge with P. berghei sporozoites in a proportion of both inbred and outbred mice. The biological activity of CelTOS-specific antibodies against the malaria parasite is likely linked to the impairment of sporozoite motility and hepatocyte infectivity. The results underscore the potential of this antigen as a pre-erythrocytic vaccine candidate and demonstrate for the first time a malaria vaccine that is cross-protective between species. 相似文献126.
Synonymous codon replacement can change protein structure and function, indicating that protein structure depends on DNA sequence. During heterologous protein expression, low expression or formation of insoluble aggregates may be attributable to differences in synonymous codon usage between expression and natural hosts. This discordance may be particularly important during translation of the domain boundaries (link/end segments) that separate elements of higher ordered structure. Within such regions, ribosomal progression slows as the ribosome encounters clusters of infrequently used codons that preferentially encode a subset of amino acids. To replicate the modulation of such localized translation rates during heterologous expression, we used known relationships between codon usage frequencies and secondary protein structure to develop an algorithm ("codon harmonization") for identifying regions of slowly translated mRNA that are putatively associated with link/end segments. It then recommends synonymous replacement codons having usage frequencies in the heterologous expression host that are less than or equal to the usage frequencies of native codons in the native expression host. For protein regions other than these putative link/end segments, it recommends synonymous substitutions with codons having usage frequencies matched as nearly as possible to the native expression system. Previous application of this algorithm facilitated E. coli expression, manufacture and testing of two Plasmodium falciparum vaccine candidates. Here we describe the algorithm in detail and apply it to E. coli expression of three additional P. falciparum proteins. Expression of the "recoded" genes exceeded that of the native genes by 4- to 1,000-fold, representing levels suitable for vaccine manufacture. The proteins were soluble and reacted with a variety of functional conformation-specific mAbs suggesting that they were folded properly and had assumed native conformation. Codon harmonization may further provide a general strategy for improving the expression of soluble functional proteins during heterologous expression in hosts other than E. coli. 相似文献
127.
Susana Beatriz Etcheverry Evelina Gloria Ferrer Luciana Naso Josefina Rivadeneira Victoria Salinas Patricia Ana María Williams 《Journal of biological inorganic chemistry》2008,13(3):435-447
Vanadium compounds are known for a variety of pharmacological properties. Many of them display antitumoral and osteogenic
effects in several cell lines. Free radicals induce the development of tumoral processes. Natural polyphenols such as flavonoids
have antioxidant properties since they scavenge different free radicals. For these reasons it is interesting to investigate
the effects of a new complex generated between the vanadyl(IV) cation and the flavonoid hesperidin. The complex has been synthesized
and characterized by physicochemical methods. Spectroscopic analysis revealed a 1:1 stoichiometry of ligand:VO and coordination
by deprotonated cis-hydroxyl groups to the disaccharide moiety of the ligand. The complex improves the superoxide dismutase (SOD)-like activity
of the ligand, but the scavenging of other radicals tested does not change upon complexation. When tested on two tumoral cell
lines in culture (one of them derived from a rat osteosarcoma UMR106 and the other from human colon adenocarcinoma Caco-2),
the complex enhanced the antiproliferative effects of the free ligand, and this effect correlated with the morphological alterations
toward apoptosis. Also, on the osteoblastic cell line the complex stimulated cell proliferation and collagen type I production
at low concentrations. At higher doses the complex behaved as a cytotoxic compound for the osteoblasts. 相似文献
128.
Aiming at improving classification and taxonomy of Gram-negative phytopathogenic bacteria, we studied the structure of the lipopolysaccharide of Ralstonia solanacearum. Mild acid hydrolysis of the lipopolysaccharide of strain Toudk-2 followed by gel chromatography resulted in an O-polysaccharide and two oligosaccharide fractions. The smallest-size oligosaccharide fraction was studied by sugar analysis, high-resolution electrospray ionization mass spectrometry, and, after fractionation by anion-exchange chromatography on HiTrap Q, by one- and two-dimensional (1)H and (13)C NMR spectroscopy. It was found that the isolated oligosaccharides consist of the lipopolysaccharide core with one O-polysaccharide repeat (O-unit) attached. The core exists in two major glycoforms differing from each other in a lateral octulosonic acid residue, which is either D-glycero-D-talo-oct-2-ulosonic acid or 3-deoxy-D-manno-oct-2-ulosonic acid. A peculiar feature of the core is the occurrence of 4-amino-4-deoxy-L-arabinose nonstoichiometrically linked to a heptose residue. The full structures of the core and the biological O-unit as well as the site of the attachment of the O-unit to the core were established. 相似文献
129.
Costanzo E Gulino M Lanzanò L Musumeci F Scordino A Tudisco S Sui L 《European biophysics journal : EBJ》2008,37(2):235-238
Time resolved spectral components of delayed luminescence (DL) from single dry soybean seeds were measured using a device
with single photon sensitivity. The seeds were aged by a thermal treatment to change their viability. A correlation was observed
between the seeds viability and some DL parameters, i.e. the total number of photons emitted and the relative decay probability
of excited states. This relevant result confirms the close connection between the state of biological systems and their DL,
and it can allow the development of a quick selection technique for single dry seeds, a goal impossible up today. 相似文献
130.
Fedonenko YP Konnova ON Zatonsky GV Shashkov AS Konnova SA Zdorovenko EL Ignatov VV Knirel YA 《Carbohydrate research》2004,339(10):1813-1816
The O-polysaccharide was isolated from the lipopolysaccharide of the plant-growth-promoting bacterium Azospirillum irakense KBC1 and studied by sugar and methylation analyses, Smith degradation and 1H and 13C NMR spectroscopy, including 1H, 13C HSQC and NOESY experiments for linkage and sequence analysis. The following structure of the branched hexasaccharide repeating unit of the O-polysaccharide with an unusually long side chain was established: [carbohydrate structure: see text]. 相似文献