全文获取类型
收费全文 | 76篇 |
免费 | 4篇 |
出版年
2017年 | 1篇 |
2016年 | 3篇 |
2015年 | 4篇 |
2014年 | 3篇 |
2013年 | 3篇 |
2012年 | 4篇 |
2011年 | 1篇 |
2010年 | 1篇 |
2009年 | 2篇 |
2008年 | 2篇 |
2007年 | 4篇 |
2006年 | 3篇 |
2004年 | 2篇 |
2003年 | 4篇 |
2002年 | 3篇 |
2001年 | 2篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1998年 | 3篇 |
1997年 | 1篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 4篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1972年 | 1篇 |
1971年 | 2篇 |
1969年 | 1篇 |
排序方式: 共有80条查询结果,搜索用时 15 毫秒
21.
Background
Unravelling the path from genotype to phenotype, as it is influenced by an organism's environment, is one of the central goals in biology. Gene expression profiling by means of microarrays has become very prominent in this endeavour, although resources exist only for relatively few model systems. As genomics has matured into a comparative research program, expression profiling now also provides a powerful tool for non-traditional model systems to elucidate the molecular basis of complex traits. 相似文献22.
Nibbering CP Frederik PM van Berge-Henegouwen GP van Veen HA van Marle J van Erpecum KJ 《Biochimica et biophysica acta》2002,1583(2):213-220
To examine physical-chemical aspects of bile salt-phospholipid interactions that could contribute to preferential phosphatidylcholine (PC) secretion into bile, we have compared transitions between vesicles and micelles in model systems containing taurocholate (TC) and either egg-yolk PC (EYPC), egg-yolk sphingomyelin (EYSM), buttermilk SM (BMSM) or dipalmitoyl PC (DPPC). Phase transitions from micelles to vesicles were observed at 4-fold dilution of serially diluted EYPC/TC systems, but not earlier than at 16-fold dilution of SM/TC or DPPC/TC systems, indicating lower concentrations of the detergent required for micellization in the case of SM or DPPC. Cryo-transmission electron microscopy of phase transitions initiated by addition of TC to phospholipid vesicles revealed extremely long SM-containing intermediate structures, but shorter EYPC-containing intermediate structures. Again, larger amounts of bile salt were required to induce phase transitions in the case of EYPC compared to SM. Sizes of TC-phospholipid micelles increased progressively upon increasing phospholipid contents in the rank order: DPPC-TC相似文献
23.
Kim Vriens Tanne L. Cools Peta J. Harvey David J. Craik Pieter Spincemaille David Cassiman Annabel Braem Jozef Vleugels Peter H. Nibbering Jan Wouter Drijfhout Barbara De Coninck Bruno P. A. Cammue Karin Thevissen 《PloS one》2015,10(8)
Plant defensins are small, cysteine-rich peptides with antifungal activity against a broad range of yeast and fungi. In this study we investigated the antibiofilm activity of a plant defensin from coral bells (Heuchera sanguinea), i.e. HsAFP1. To this end, HsAFP1 was heterologously produced using Pichia pastoris as a host. The recombinant peptide rHsAFP1 showed a similar antifungal activity against the plant pathogen Fusarium culmorum as native HsAFP1 purified from seeds. NMR analysis revealed that rHsAFP1 consists of an α-helix and a triple-stranded antiparallel β-sheet stabilised by four intramolecular disulfide bonds. We found that rHsAFP1 can inhibit growth of the human pathogen Candida albicans as well as prevent C. albicans biofilm formation with a BIC50 (i.e. the minimum rHsAFP1 concentration required to inhibit biofilm formation by 50% as compared to control treatment) of 11.00 ± 1.70 μM. As such, this is the first report of a plant defensin exhibiting inhibitory activity against fungal biofilms. We further analysed the potential of rHsAFP1 to increase the activity of the conventional antimycotics caspofungin and amphotericin B towards C. albicans. Synergistic effects were observed between rHsAFP1 and these compounds against both planktonic C. albicans cells and biofilms. Most notably, concentrations of rHsAFP1 as low as 0.53 μM resulted in a synergistic activity with caspofungin against pre-grown C. albicans biofilms. rHsAFP1 was found non-toxic towards human HepG2 cells up to 40 μM, thereby supporting the lack of a general cytotoxic activity as previously reported for HsAFP1. A structure-function study with 24-mer synthetic peptides spanning the entire HsAFP1 sequence revealed the importance of the γ-core and its adjacent regions for HsAFP1 antibiofilm activity. These findings point towards broad applications of rHsAFP1 and its derivatives in the field of antifungal and antibiofilm drug development. 相似文献
24.
25.
Letícia Muraro Wildner Maria Luiza Bazzo Susie Coutinho Liedke Christiane Louren?o Nogueira Gabriela Segat Simone Gon?alves Senna Aline Daiane Schlindwein Jaquelline Germano de Oliveira Darcita B Rovaris Claudio A Bonjardim Erna G Kroon Paulo CP Ferreira 《Memórias do Instituto Oswaldo Cruz》2014,109(3):356-361
The identification of mycobacteria is essential because tuberculosis (TB) and
mycobacteriosis are clinically indistinguishable and require different therapeutic
regimens. The traditional phenotypic method is time consuming and may last up to 60
days. Indeed, rapid, affordable, specific and easy-to-perform identification methods
are needed. We have previously described a polymerase chain reaction-based method
called a mycobacteria mobility shift assay (MMSA) that was designed for
Mycobacterium tuberculosis complex (MTC) and nontuberculous mycobacteria
(NTM) species identification. The aim of this study was to assess the MMSA for the
identification of MTC and NTM clinical isolates and to compare its performance with
that of the PRA-hsp65 method. A total of 204 clinical isolates (102
NTM and 102 MTC) were identified by the MMSA and PRA-hsp65. For
isolates for which these methods gave discordant results, definitive species
identification was obtained by sequencing fragments of the 16S rRNA and
hsp65 genes. Both methods correctly identified all MTC isolates. Among
the NTM isolates, the MMSA alone assigned 94 (92.2%) to a complex or species, whereas
the PRA-hsp65 method assigned 100% to a species. A 91.5% agreement
was observed for the 94 NTM isolates identified by both methods. The MMSA provided
correct identification for 96.8% of the NTM isolates compared with 94.7% for
PRA-hsp65. The MMSA is a suitable auxiliary method for routine
use for the rapid identification of mycobacteria. 相似文献
26.
de Breij A Eveillard M Dijkshoorn L van den Broek PJ Nibbering PH Joly-Guillou ML 《PloS one》2012,7(2):e30673
Despite many reports documenting its epidemicity, little is known on the interaction of Acinetobacter baumannii with its host. To deepen our insight into this relationship, we studied persistence of and host response to different A. baumannii strains including representatives of the European (EU) clones I-III in a mouse pneumonia model. Neutropenic mice were inoculated intratracheally with five A. baumannii strains and an A. junii strain and at several days morbidity, mortality, bacterial counts, airway inflammation, and chemo- and cytokine production in lungs and blood were determined. A. baumannii RUH875 and RUH134 (EU clone I and II, respectively) and sporadic strain LUH8326 resulted in high morbidity/mortality, whereas A. baumannii LUH5875 (EU clone III, which is less widespread than clone I and II) caused less symptoms. A. baumannii type strain RUH3023(T) and A. junii LUH5851 did not cause disease. All strains, except A. baumannii RUH3023(T) and A. junii LUH5851, survived and multiplied in the lungs for several days. Morbidity and mortality were associated with the severity of lung pathology and a specific immune response characterized by low levels of anti-inflammatory (IL-10) and specific pro-inflammatory (IL-12p40 and IL-23) cytokines at the first day of infection. Altogether, a striking difference in behaviour among the A. baumannii strains was observed with the clone I and II strains being most virulent, whereas the A. baumannii type strain, which is frequently used in virulence studies appeared harmless. 相似文献
27.
Marcilio CP de Souto Ivan G Costa Daniel SA de Araujo Teresa B Ludermir Alexander Schliep 《BMC bioinformatics》2008,9(1):497
Background
The use of clustering methods for the discovery of cancer subtypes has drawn a great deal of attention in the scientific community. While bioinformaticians have proposed new clustering methods that take advantage of characteristics of the gene expression data, the medical community has a preference for using "classic" clustering methods. There have been no studies thus far performing a large-scale evaluation of different clustering methods in this context. 相似文献28.
The purpose of the present study was to compare the phenotype of tissue macrophages with that of their precursors in the bone marrow and blood. The phenotype was determined on the basis of the quantitative binding of monoclonal antibodies to cell-surface antigens (antigen F4/80, complement receptor III, Fc receptor II, Ia antigen, common leukocyte antigen, and Mac-2 and Mac-3 antigens) on individual mononuclear phagocytes. Monoclonal antibody binding to cells, detected by the biotin-avidin immunoperoxidase procedure, was quantitated by cytophotometric determination of the amount of enzyme reaction product on cells. The results of this quantitation are expressed as the median of the specific absorbance per unit of cell-surface area (0.25 micron2) and per cell. Shortly after collection of the mononuclear phagocytes, binding of all monoclonal antibodies except those directed against the common leukocyte and Mac-2 antigens to peritoneal macrophages was enhanced compared with binding to blood monocytes; for alveolar macrophages we found reduced binding of monoclonal antibodies F4/80 and M1/70 (complement receptor III) and enhanced binding of monoclonal antibodies with specificity for the common leukocyte antigen and Mac-2 and Mac-3 antigens. The results obtained with cultured mononuclear phagocytes show that during the development from monoblast to tissue macrophages, monoclonal antibody binding to the various types of mononuclear phagocyte, expressed per unit of cell-surface area, was not significantly altered except that of M3/38 (Mac-2 antigen) to peritoneal macrophages and that of F4/80 and M1/70 (complement receptor III) to alveolar macrophages. Expressed on a per cell basis, the results show an increase in the binding of all monoclonal antibodies except those directed against the Fc receptor II and Mac-3 antigen during the development from promonocytes to peritoneal macrophages; binding of most monoclonal antibodies to alveolar macrophages was considerably lower than that to blood monocytes. It is concluded that the expression of the various cell-surface antigens alters during mononuclear phagocyte differentiation. The expression changed also during culture, although distinct patterns of alteration could not be distinguished. 相似文献
29.
Microsporidia, amitochondrial protists, possess a 70-kDa heat shock protein gene of mitochondrial evolutionary origin 总被引:13,自引:3,他引:10
Peyretaillade E; Broussolle V; Peyret P; Metenier G; Gouy M; Vivares CP 《Molecular biology and evolution》1998,15(6):683-689
An intronless gene encoding a protein of 592 amino acid residues with
similarity to 70-kDa heat shock proteins (HSP70s) has been cloned and
sequenced from the amitochondrial protist Encephalitozoon cuniculi (phylum
Microsporidia). Southern blot analyses show the presence of a single gene
copy located on chromosome XI. The encoded protein exhibits an N-terminal
hydrophobic leader sequence and two motifs shared by proteobacterial and
mitochondrially expressed HSP70 homologs. Phylogenetic analysis using
maximum likelihood and evolutionary distances place the E. cuniculi
sequence in the cluster of mitochondrially expressed HSP70s, with a higher
evolutionary rate than those of homologous sequences. Similar results were
obtained after cloning a fragment of the homologous gene in the closely
related species E. hellem. The presence of a nuclear targeting signal-like
sequence supports a role of the Encephalitozoon HSP70 as a molecular
chaperone of nuclear proteins. No evidence for cytosolic or endoplasmic
reticulum forms of HSP70 was obtained through PCR amplification. These data
suggest that Encephalitozoon species have evolved from an ancestor bearing
mitochondria, which is in disagreement with the postulated presymbiotic
origin of Microsporidia. The specific role and intracellular localization
of the mitochondrial HSP70-like protein remain to be elucidated.
相似文献
30.