全文获取类型
收费全文 | 641篇 |
免费 | 61篇 |
出版年
2022年 | 5篇 |
2021年 | 22篇 |
2020年 | 8篇 |
2019年 | 8篇 |
2018年 | 8篇 |
2017年 | 31篇 |
2016年 | 15篇 |
2015年 | 20篇 |
2014年 | 30篇 |
2013年 | 26篇 |
2012年 | 37篇 |
2011年 | 34篇 |
2010年 | 32篇 |
2009年 | 18篇 |
2008年 | 26篇 |
2007年 | 21篇 |
2006年 | 18篇 |
2005年 | 23篇 |
2004年 | 16篇 |
2003年 | 20篇 |
2002年 | 15篇 |
2001年 | 8篇 |
2000年 | 21篇 |
1999年 | 13篇 |
1998年 | 10篇 |
1997年 | 7篇 |
1995年 | 6篇 |
1994年 | 5篇 |
1992年 | 11篇 |
1991年 | 13篇 |
1990年 | 13篇 |
1989年 | 12篇 |
1988年 | 7篇 |
1987年 | 14篇 |
1986年 | 8篇 |
1985年 | 11篇 |
1984年 | 11篇 |
1983年 | 10篇 |
1982年 | 12篇 |
1981年 | 7篇 |
1980年 | 7篇 |
1979年 | 3篇 |
1978年 | 5篇 |
1977年 | 6篇 |
1976年 | 7篇 |
1975年 | 7篇 |
1974年 | 3篇 |
1973年 | 6篇 |
1972年 | 4篇 |
1960年 | 3篇 |
排序方式: 共有702条查询结果,搜索用时 31 毫秒
621.
622.
Júlio Santos Maria Jo?o Gouveia Nuno Vale Maria de Lurdes Delgado Ana Gon?alves José M. Teixeira. da Silva Cristiano Oliveira Pedro Xavier Paula Gomes Lúcio L. Santos Carlos Lopes Alberto Barros Gabriel Rinaldi Paul J. Brindley José M. Correia da Costa Mário Sousa Mónica C. Botelho 《PloS one》2014,9(5)
Background
Schistosomiasis is a neglected tropical disease, endemic in 76 countries, that afflicts more than 240 million people. The impact of schistosomiasis on infertility may be underestimated according to recent literature. Extracts of Schistosoma haematobium include estrogen-like metabolites termed catechol-estrogens that down regulate estrogen receptors alpha and beta in estrogen responsive cells. In addition, schistosome derived catechol-estrogens induce genotoxicity that result in estrogen-DNA adducts. These catechol estrogens and the catechol-estrogen-DNA adducts can be isolated from sera of people infected with S. haematobium. The aim of this study was to study infertility in females infected with S. haematobium and its association with the presence of schistosome-derived catechol-estrogens.Methodology/Principal Findings
A cross-sectional study was undertaken of female residents of a region in Bengo province, Angola, endemic for schistosomiasis haematobia. Ninety-three women and girls, aged from two (parents interviewed) to 94 years were interviewed on present and previous urinary, urogenital and gynecological symptoms and complaints. Urine was collected from the participants for egg-based parasitological assessment of schistosome infection, and for liquid chromatography diode array detection electron spray ionization mass spectrometry (LC/UV-DAD/ESI-MSn) to investigate estrogen metabolites in the urine. Novel estrogen-like metabolites, potentially of schistosome origin, were detected in the urine of participants who were positive for eggs of S. haematobium, but not detected in urines negative for S. haematobium eggs. The catechol-estrogens/ DNA adducts were significantly associated with schistosomiasis (OR 3.35; 95% CI 2.32–4.84; P≤0.001). In addition, presence of these metabolites was positively associated with infertility (OR 4.33; 95% CI 1.13–16.70; P≤0.05).Conclusions/Significance
Estrogen metabolites occur widely in diverse metabolic pathways. In view of the statistically significant association between catechol-estrogens/ DNA adducts and self-reported infertility, we propose that an estrogen-DNA adduct mediated pathway in S. haematobium-induced ovarian hormonal deregulation could be involved. In addition, the catechol-estrogens/ DNA adducts described here represent potential biomarkers for schistosomiasis haematobia. 相似文献623.
Joel A. Mathews Alison S. Williams Jeffrey D. Brand Allison P. Wurmbrand Lucas Chen Fernanda MC. Ninin Huiqing Si David I. Kasahara Stephanie A. Shore 《PloS one》2014,9(5)
Ozone is an air pollutant that causes pulmonary symptoms. In mice, ozone exposure causes pulmonary injury and increases bronchoalveolar lavage macrophages and neutrophils. We have shown that IL-17A is important in the recruitment of neutrophils after subacute ozone exposure (0.3 ppm for 24–72 h). We hypothesized that γδ T cells are the main producers of IL-17A after subacute ozone. To explore this hypothesis we exposed wildtype mice and mice deficient in γδ T cells (TCRδ−/−) to ozone or room air. Ozone-induced increases in BAL macrophages and neutrophils were attenuated in TCRδ−/− mice. Ozone increased the number of γδ T cells in the lungs and increased pulmonary Il17a mRNA expression and the number of IL-17A+ CD45+ cells in the lungs and these effects were abolished in TCRδ−/− mice. Ozone-induced increases in factors downstream of IL-17A signaling, including G-CSF, IL-6, IP-10 and KC were also decreased in TCRδ−/− versus wildtype mice. Neutralization of IL-17A during ozone exposure in wildtype mice mimicked the effects of γδ T cell deficiency. TNFR2 deficiency and etanercept, a TNFα antagonist, also reduced ozone-induced increases in Il17a mRNA, IL-17A+ CD45+ cells and BAL G-CSF as well as BAL neutrophils. TNFR2 deficient mice also had decreased ozone-induced increases in Ccl20, a chemoattractant for IL-17A+ γδ T cells. Il17a mRNA and IL-17A+ γδ T cells were also lower in obese Cpefat versus lean WT mice exposed to subacute ozone, consistent with the reduced neutrophil recruitment observed in the obese mice. Taken together, our data indicate that pulmonary inflammation induced by subacute ozone requires γδ T cells and TNFα-dependent recruitment of IL-17A+ γδ T cells to the lung. 相似文献
624.
625.
Opportunities for genetic exchange are abundant between bacteria and foreign genetic elements (FGEs) such as conjugative plasmids, transposable elements and bacteriophages. The genetic novelty that may arise from these forms of genetic exchange is potentially beneficial to bacterial hosts, but there are also potential costs, which may be considerable in the case of phage infection. Some bacterial resistance mechanisms target both beneficial and deleterious forms of genetic exchange. Using a general epidemiological model, we explored under which conditions such resistance mechanisms may evolve. We considered a population of hosts that may be infected by FGEs that either confer a benefit or are deleterious to host fitness, and we analysed the epidemiological and evolutionary outcomes of resistance evolving under different cost/benefit scenarios. We show that the degree of co‐infection between these two types of infection is particularly important in determining the evolutionarily stable level of host resistance. We explore these results using the example of CRISPR‐Cas, a form of bacterial immunity that targets a variety of FGEs, and we show the potential role of bacteriophage infection in selecting for resistance mechanisms that in turn limit the acquisition of plasmid‐borne antibiotic resistance. Finally, beyond microbes, we discuss how endosymbiotic associations may have shaped the evolution of host immune responses to pathogens. 相似文献
626.
Christopher P. Toret Michael V. D’Ambrosio Ronald D. Vale Michael A. Simon W. James Nelson 《The Journal of cell biology》2014,204(2):265-279
Cadherins and associated catenins provide an important structural interface
between neighboring cells, the actin cytoskeleton, and intracellular signaling
pathways in a variety of cell types throughout the Metazoa. However, the full
inventory of the proteins and pathways required for cadherin-mediated adhesion
has not been established. To this end, we completed a genome-wide
(∼14,000 genes) ribonucleic acid interference (RNAi) screen that targeted
Ca2+-dependent adhesion in DE-cadherin–expressing
Drosophila melanogaster S2 cells in suspension culture.
This novel screen eliminated Ca2+-independent cell–cell
adhesion, integrin-based adhesion, cell spreading, and cell migration. We
identified 17 interconnected regulatory hubs, based on protein functions and
protein–protein interactions that regulate the levels of the core
cadherin–catenin complex and coordinate cadherin-mediated
cell–cell adhesion. Representative proteins from these hubs were analyzed
further in Drosophila oogenesis, using targeted germline RNAi,
and adhesion was analyzed in Madin–Darby canine kidney mammalian
epithelial cell–cell adhesion. These experiments reveal roles for a
diversity of cellular pathways that are required for cadherin function in
Metazoa, including cytoskeleton organization, cell–substrate
interactions, and nuclear and cytoplasmic signaling. 相似文献
627.
Rita M. Godinho Carlos Vale Miguel Caetano Luis C. Alves Teresa Pinheiro 《Plant and Soil》2014,376(1-2):129-137
Aim
This study presents a micrometre-scale map of the elemental distribution within roots and surrounding sediment of Halimione portulacoides of a contaminated salt marsh in the Tagus estuary.Methods
Microprobe particle induced X-ray emission analysis was performed in sediment slices containing roots with tubular rhizoconcretions attached to host sediments.Results
Strong concentration gradients were found particularly in the inner part of rhizoconcretions adjacent to the root wall. Local enrichment was observed in sediment interstices with Fe precipitates and other associated elements. A maximum of 55 % of Fe was measured near the concretion–root interface, with a decrease to <5 % in the host sediment. Maximum concentrations of P (3 %), As (1,200 μg g?1) and Zn (3,000 μg g?1) were registered in concretions, one order of magnitude above the values of the host sediment. The elemental concentration profiles across roots showed that the epidermis was an efficient selective barrier to the entrance of elements. Fe and As were retained in the epidermis. The highest Cu and Zn concentrations were also observed in the epidermis. However, the concentrations of Mn, Cu and Zn increased in the inner root.Conclusions
As and Fe were mostly retained in the concretion, whereas P, Mn, Cu and Zn were mobilised by the root. 相似文献628.
Background
A central hypothesis in the evolutionary ecology of parasitism is that trade-offs exist between resistance to parasites and other fitness components such as fecundity, growth, survival, and predator avoidance, or resistance to other parasites. These trade-offs are called costs of resistance. These costs fall into two broad categories: constitutive costs of resistance, which arise from a negative genetic covariance between immunity and other fitness-related traits, and inducible costs of resistance, which are the physiological costs incurred by hosts when mounting an immune response. We sought to study inducible costs in depth using the crustacean Daphnia magna and its bacterial parasite Pasteuria ramosa. 相似文献629.
New saxitoxin analogues in the marine environment: developments in toxin chemistry,detection and biotransformation during the 2000s 总被引:1,自引:0,他引:1
Paulo Vale 《Phytochemistry Reviews》2010,9(4):525-535
Scientific study of paralytic shellfish poisoning toxins (PSTs) started in the early XXth century. In the 1920s it was understood
the link between the toxicity observed in mussels with certain microalgae species. The poison was eventually purified from
the clam Saxidomus giganteus, taking its name from it: saxitoxin (STX). Along the 1970s and 1980s it was understood that other STX analogues existed,
both in dinoflagellates and bivalves. These were grouped into three major occurring families: the carbamate, N-sulfocarbamoyl and decarbamoyl, depending on the variation of the side chain of the tetrahydropurine core. The deoxydecarbamoyl
family was additionally recognised in the dinoflagellate Gymnodinium catenatum. Chemical research into these STX analogues was conducted worldwide during the 1990s mainly by HPLC with pre- or post-column
oxidation and fluorescence detection. Implementation of fluorescence detection with spectral capabilities and mass spectrometry
detection during the 2000s led to the recognition of new analogues. Metabolites originated by single or double hydroxylation
at C11 position were found in mussels, and later suspected in other bivalves. Designated M1-M4, these present very low fluorescence,
and can only be studied resorting to HILIC-MS. Three hydroxybenzoate analogues were characterised as an important toxin fraction
of the dinoflagellate Gymnodinium catenatum, and named GC1-GC3. Later, many more analogues were suspected: the corresponding N1-hydroxyl variants of GC1-GC3 (GC4-GC6),
di-hydroxybenzoate variants (GC1a-GC6a), and sulphate-benzoate variants (GC1b-GC6b). In bivalves, carbamoylase activity renders
these analogues into decarbamoyl analogues. Other compounds with PST-like characteristics have been detected in bivalves from
Angola, Argentina and Vietnam. Today, the range of naturally occurring STX derivatives, both in marine and freshwater environments,
accounts to more than fifty structural variants. This poses a problem for carrying out food safety analysis based solely in
chemical methods. Fortunately, most modifications to the side chain of the tetrahydropurine core result in diminished toxicity. 相似文献
630.