全文获取类型
收费全文 | 435篇 |
免费 | 49篇 |
出版年
2023年 | 2篇 |
2021年 | 11篇 |
2020年 | 4篇 |
2019年 | 11篇 |
2018年 | 9篇 |
2017年 | 15篇 |
2016年 | 14篇 |
2015年 | 24篇 |
2014年 | 21篇 |
2013年 | 16篇 |
2012年 | 24篇 |
2011年 | 23篇 |
2010年 | 15篇 |
2009年 | 14篇 |
2008年 | 20篇 |
2007年 | 19篇 |
2006年 | 17篇 |
2005年 | 14篇 |
2004年 | 11篇 |
2003年 | 11篇 |
2002年 | 9篇 |
2001年 | 11篇 |
2000年 | 16篇 |
1999年 | 11篇 |
1998年 | 13篇 |
1997年 | 11篇 |
1996年 | 9篇 |
1995年 | 5篇 |
1994年 | 5篇 |
1993年 | 3篇 |
1992年 | 5篇 |
1991年 | 2篇 |
1990年 | 7篇 |
1989年 | 7篇 |
1988年 | 6篇 |
1987年 | 4篇 |
1986年 | 4篇 |
1985年 | 12篇 |
1984年 | 3篇 |
1983年 | 5篇 |
1982年 | 4篇 |
1979年 | 4篇 |
1978年 | 2篇 |
1977年 | 8篇 |
1976年 | 6篇 |
1975年 | 4篇 |
1974年 | 3篇 |
1972年 | 3篇 |
1968年 | 1篇 |
1967年 | 2篇 |
排序方式: 共有484条查询结果,搜索用时 15 毫秒
51.
Dahl JL Arora K Boshoff HI Whiteford DC Pacheco SA Walsh OJ Lau-Bonilla D Davis WB Garza AG 《Journal of bacteriology》2005,187(7):2439-2447
The modification of metabolic pathways to allow for a dormant lifestyle appears to be an important feature for the survival of pathogenic bacteria within their host. One regulatory mechanism for persistent Mycobacterium tuberculosis infections is the stringent response. In this study, we analyze the stringent response of a nonpathogenic, saprophytic mycobacterial species, Mycobacterium smegmatis. The use of M. smegmatis as a tool for studying the mycobacterial stringent response was demonstrated by measuring the expression of two M. tuberculosis genes, hspX and eis, in M. smegmatis in the presence and absence of rel(Msm). The stringent response plays a role in M. smegmatis cellular and colony formation that is suggestive of changes in the bacterial cell wall structure. 相似文献
52.
Orsomando G de la Garza RD Green BJ Peng M Rea PA Ryan TJ Gregory JF Hanson AD 《The Journal of biological chemistry》2005,280(32):28877-28884
gamma-Glutamyl hydrolase (GGH, EC 3.4.19.9) catalyzes removal of the polyglutamyl tail from folyl and p-aminobenzoyl polyglutamates. Plants typically have one or a few GGH genes; Arabidopsis has three, tandemly arranged on chromosome 1, which encode proteins with predicted secretory pathway signal peptides. Two representative Arabidopsis GGH proteins, AtGGH1 and AtGGH2 (the At1g78660 and At1g78680 gene products, respectively) were expressed in truncated form in Escherichia coli and purified. Both enzymes were active as dimers, had low K(m) values (0.5-2 microm) for folyl and p-aminobenzoyl pentaglutamates, and acted as endopeptidases. However, despite 80% sequence identity, they differed in that AtGGH1 cleaved pentaglutamates, mainly to di- and triglutamates, whereas AtGGH2 yielded mainly monoglutamates. Analysis of subcellular fractions of pea leaves and red beet roots established that GGH activity is confined to the vacuole and that this activity, if not so sequestered, would deglutamylate all cellular folylpolyglutamates within minutes. Purified pea leaf vacuoles contained an average of 20% of the total cellular folate compared with approximately 50 and approximately 10%, respectively, in mitochondria and chloroplasts. The main vacuolar folate was 5-methyltetrahydrofolate, of which 51% was polyglutamylated. In contrast, the principal mitochondrial and chloroplastic forms were 5-formyl- and 5,10-methenyltetrahydrofolate polyglutamates, respectively. In beet roots, 16-60% of the folate was vacuolar and was again mainly 5-methyltetrahydrofolate, of which 76% was polyglutamylated. These data point to a hitherto unsuspected role for vacuoles in folate storage. Furthermore, the paradoxical co-occurrence of GGH and folylpolyglutamates in vacuoles implies that the polyglutamates are somehow protected from GGH attack. 相似文献
53.
54.
Héctor Flores-Villase?or Adrian Canizalez-Román Magda Reyes-Lopez Kamram Nazmi Mireya de la Garza Jorge Zazueta-Beltrán Nidia León-Sicairos Jan G. M. Bolscher 《Biometals》2010,23(3):569-578
Increased prevalence of antibiotic-resistant bacteria has become a major threat to the health sector worldwide due to their
virulence, limited therapeutic options and distribution in both hospital and community settings. Discovery and development
of new agents to combat antibiotic-resistant bacteria is thus needed. This study therefore aimed to evaluate the ability of
bovine lactoferrin (LF), peptides from two antimicrobial domains lactoferricin B (LFcin17-30) and lactoferrampin (LFampin265-284)
and a chimeric construct (LFchimera) containing both peptides, as potential bactericidal agents against clinical isolates
of antibiotic-resistant Staphylococcus aureus and Escherichia coli. Results in kinetics of growth show that LF chimera and peptides inhibited the growth of both bacterial species. By confocal
microscopy and flow cytometry it was observed that LF and FITC-labeled peptides are able to interact with these bacteria and
cause membrane permeabilization, as monitored by propidium iodide staining, these effects were decreased by preincubation
with lipopolysaccharide in E. coli. By electron microscopy, a clear cellular damage was observed in bacteria after treatments with LFchimera and peptides, suggesting
that interaction and membrane disruption are probably involved as a mechanism of action. In conclusion, results show that
LFchimera, LF and peptides have potential as bactericidal agents in the antibiotic-resistant strains of S.
aureus and E. coli and also the work strongly suggest that LFcin17-30 and LFampin265-284 acts synergistically with antibiotics against multidrug
resistant EPEC and MRSA in vitro. 相似文献
55.
Background
It has been argued that multibreed animal models should include a heterogeneous covariance structure. However, the estimation of the (co)variance components is not an easy task, because these parameters can not be factored out from the inverse of the additive genetic covariance matrix. An alternative model, based on the decomposition of the genetic covariance matrix by source of variability, provides a much simpler formulation. In this study, we formalize the equivalence between this alternative model and the one derived from the quantitative genetic theory. Further, we extend the model to include maternal effects and, in order to estimate the (co)variance components, we describe a hierarchical Bayes implementation. Finally, we implement the model to weaning weight data from an Angus × Hereford crossbred experiment.Methods
Our argument is based on redefining the vectors of breeding values by breed origin such that they do not include individuals with null contributions. Next, we define matrices that retrieve the null-row and the null-column pattern and, by means of appropriate algebraic operations, we demonstrate the equivalence. The extension to include maternal effects and the estimation of the (co)variance components through the hierarchical Bayes analysis are then straightforward. A FORTRAN 90 Gibbs sampler was specifically programmed and executed to estimate the (co)variance components of the Angus × Hereford population.Results
In general, genetic (co)variance components showed marginal posterior densities with a high degree of symmetry, except for the segregation components. Angus and Hereford breeds contributed with 50.26% and 41.73% of the total direct additive variance, and with 23.59% and 59.65% of the total maternal additive variance. In turn, the contribution of the segregation variance was not significant in either case, which suggests that the allelic frequencies in the two parental breeds were similar.Conclusion
The multibreed maternal animal model introduced in this study simplifies the problem of estimating (co)variance components in the framework of a hierarchical Bayes analysis. Using this approach, we obtained for the first time estimates of the full set of genetic (co)variance components. It would be interesting to assess the performance of the procedure with field data, especially when interbreed information is limited. 相似文献56.
57.
CbgA, a protein involved in cortex formation and stress resistance in Myxococcus xanthus spores 下载免费PDF全文
Tengra FK Dahl JL Dutton D Caberoy NB Coyne L Garza AG 《Journal of bacteriology》2006,188(23):8299-8302
CbgA plays a role in cortex formation and the acquisition of a subset of stress resistance properties in Myxococcus xanthus spores. The cbgA mutant produces spores with thin or no cortex layers, and these spores are more sensitive to heat and sodium dodecyl sulfate than their wild-type counterparts. 相似文献
58.
RP Tucker K Drabikowski JF Hess J Ferralli R Chiquet-Ehrismann JC Adams 《BMC evolutionary biology》2006,6(1):60-17
Background
Tenascins are a family of glycoproteins found primarily in the extracellular matrix of embryos where they help to regulate cell proliferation, adhesion and migration. In order to learn more about their origins and relationships to each other, as well as to clarify the nomenclature used to describe them, the tenascin genes of the urochordate Ciona intestinalis, the pufferfish Tetraodon nigroviridis and Takifugu rubripes and the frog Xenopus tropicalis were identified and their gene organization and predicted protein products compared with the previously characterized tenascins of amniotes. 相似文献59.
León-Sicairos N Martínez-Pardo L Sánchez-Hernández B de la Garza M Carrero JC 《Biochimie et biologie cellulaire》2012,90(3):435-441
Entamoeba histolytica is a protozoan parasite that causes amoebiasis, an illness that affects many people around the world. We have previously reported that lactoferrin is able to kill E. histolytica in in vitro cultures. The aim of the present study was to evaluate the therapeutic effect of orally administered bovine lactoferrin in the control of intestinal amoebiasis of susceptible C3H/HeJ mice. The results showed that 20 mg lactoferrin/kg orally administered each day for 1 week was able to eliminate the infection in 63% of the mice, since neither trophozoites nor evidence of epithelial damage and (or) swelling were found in tissue sections of the cecum. The rest of the treated animals (37%) showed a decrease in trophozoite numbers and mucus secreted to the lumen, as compared with untreated and infected mice (p < 0.05). By immunohistochemistry, the profile of secreted cytokines in the cecum revealed that infected but untreated animals showed a mixed Th1/regulatory cytokines profile, whereas the cecum of mice treated (cured) showed a Th2 cytokine profile (IL-4) and expression of the multifunctional IL-6. In addition, cytokines and increasing cecal production of total IgA antibodies were found associated with little inflammation and disease control observed in the cecum of lactoferrin-treated animals. These results suggest that oral administration of lactoferrin can control intestinal amoebic infection probably by killing amoebas or favoring their removal and reestablish the antiinflammatory intestinal environment. 相似文献
60.
Ordaz-Pichardo C León-Sicairos N Hernández-Ramírez VI Talamás-Rohana P de la Garza M 《Biochimie et biologie cellulaire》2012,90(3):425-434
Entamoeba histolytica is the causative agent of amoebiasis, a disease that produces dysentery as a result of the perforation of the large intestine. This parasite often invades other organs, primarily the liver, leading to an amoebic liver abscess (ALA), which can cause death. Metronidazole is the drug of choice for the treatment of ALA; however, it produces toxic side effects in patients. Lactoferrin (Lf) is a glycoprotein of the innate immune response that sequesters iron in the mucosae. Lf possesses immune-regulatory properties, such as antiinflammatory and antioxidant activities. Moreover, the microbicidal activity of apoLf, which lacks bound iron, has been shown. In this study, we evaluated the therapeutic effect of bovine Lf (bLf) against ALA in a model of hepatic amoebiasis in hamsters. Interestingly, hamsters treated intragastrically with Lf (2.5 mg/100 g mass) over a period of 8 days showed no clinical signs of disease and ALA was effectively decreased, with only 0.63% detectable lesion, compared with 63% in untreated animals. Furthermore, liver function and blood cells approached normal levels among those receiving bLf treatment. These results suggest that bLf may aid in the therapy of amoebiasis, likely without producing undesirable effects in patients. 相似文献