首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   1368篇
  免费   97篇
  国内免费   1篇
  2023年   7篇
  2022年   13篇
  2021年   39篇
  2020年   30篇
  2019年   29篇
  2018年   47篇
  2017年   50篇
  2016年   30篇
  2015年   72篇
  2014年   71篇
  2013年   110篇
  2012年   120篇
  2011年   107篇
  2010年   66篇
  2009年   60篇
  2008年   96篇
  2007年   69篇
  2006年   68篇
  2005年   70篇
  2004年   66篇
  2003年   58篇
  2002年   49篇
  2001年   9篇
  2000年   9篇
  1999年   7篇
  1998年   8篇
  1997年   9篇
  1996年   8篇
  1995年   8篇
  1994年   7篇
  1993年   3篇
  1992年   4篇
  1991年   5篇
  1990年   2篇
  1989年   4篇
  1988年   4篇
  1987年   4篇
  1986年   2篇
  1985年   5篇
  1984年   5篇
  1983年   5篇
  1982年   3篇
  1981年   6篇
  1980年   3篇
  1979年   4篇
  1974年   4篇
  1969年   1篇
  1968年   1篇
  1967年   2篇
  1962年   1篇
排序方式: 共有1466条查询结果,搜索用时 140 毫秒
151.
152.
BackgroundThe incidence of fungi like pathogens in hospitals varies by regions.ObjectivesOur goal was not only to record the incidence and etiology of fungaemia, but also the change during the 4 years analysed, to determine the time of detection in automated blood culture and by lysis-centrifugation, and finally to assess the gender, age and underlying disease of the patients with fungaemia.MethodsAn observational multicentre study of fungaemia was conducted in hospitals in the Mycology Network of Buenos Aires.ResultsA total of 190,920 blood cultures were processed: 182,050 automated blood culture and 8,870 lysis-centrifugation. Fungi were recovered in 1,020 episodes. The overall incidence of fungaemia was 1.72/1,000 admissions; 683 episodes were due to Candida (68%), and 325 (32%) to other fungi: 214 Cryptococcus, 105 Histoplasma, 7 Rhodotorula, 5 Trichosporon, 2 Pichia, 2 Acremonium, one Saccharomyces and one Fusarium. The incidence of candidaemia was 1.15/1,000 admissions with a wide variation between centres (0.35 to 2.65). Most Candida isolates (97%) were detected in the first 2 days of incubation. Candida albicans was recovered in 43% of the episodes. In fungaemia other than candidaemia, the predominant fungi were Cryptococcus and Histoplasma capsulatum.ConclusionsThe incidence remained stable during the study period. Fungaemia by Candida were predominant. C. albicans was involved in less than a half of the episodes. The recovery of Cryptoccocus and H. capsulatum is strongly associated with HIV patients.  相似文献   
153.
Atherosclerotic lesions are characterized by lipid-loaded macrophages (foam cells) and hypoxic regions. Although it is well established that foam cells are produced by uptake of cholesterol from oxidized LDL, we previously showed that hypoxia also promotes foam cell formation even in the absence of exogenous lipids. The hypoxia-induced lipid accumulation results from increased triglyceride biosynthesis but the exact mechanism is unknown. Our aim was to investigate the importance of glucose in promoting hypoxia-induced de novo lipid synthesis in human macrophages. In the absence of exogenous lipids, extracellular glucose promoted the accumulation of Oil Red O-stained lipid droplets in human monocyte-derived macrophages in a concentration-dependent manner. Lipid droplet accumulation was higher in macrophages exposed to hypoxia at all assessed concentrations of glucose. Importantly, triglyceride synthesis from glucose was increased in hypoxic macrophages. GLUT3 was highly expressed in macrophage-rich and hypoxic regions of human carotid atherosclerotic plaques and in macrophages isolated from these plaques. In human monocyte-derived macrophages, hypoxia increased expression of both GLUT3 mRNA and protein, and knockdown of GLUT3 with siRNA significantly reduced both glucose uptake and lipid droplet accumulation. In conclusion, we have shown that hypoxia-induced increases in glucose uptake through GLUT3 are important for lipid synthesis in macrophages, and may contribute to foam cell formation in hypoxic regions of atherosclerotic lesions.  相似文献   
154.

Background

The irritable bowel syndrome (IBS) is a functional gastrointestinal disorder whose pathogenesis is not completely understood. Its high prevalence and the considerable effects on quality of life make IBS a disease with high social cost. Recent studies suggest that low grade mucosal immune activation, increased intestinal permeability and the altered host-microbiota interactions that modulate innate immune response, contribute to the pathophysiology of IBS. However, the understanding of the precise molecular pathophysiology remains largely unknown.

Methodology and Findings

In this study our objective was to evaluate the TLR expression as a key player in the innate immune response, in the colonic mucosa of IBS patients classified into the three main subtypes (with constipation, with diarrhea or mixed). TLR2 and TLR4 mRNA expression was assessed by real time RT-PCR while TLRs protein expression in intestinal epithelial cells was specifically assessed by flow cytometry and immunofluorescence. Mucosal inflammatory cytokine production was investigated by the multiplex technology. Here we report that the IBS-Mixed subgroup displayed a significant up-regulation of TLR2 and TLR4 in the colonic mucosa. Furthermore, these expressions were localized in the epithelial cells, opening new perspectives for a potential role of epithelial cells in host-immune interactions in IBS. In addition, the increased TLR expression in IBS-M patients elicited intracellular signaling pathways resulting in increased expression of the mucosal proinflammatory cytokines IL-8 and IL1β.

Conclusions

Our results provide the first evidence of differential expression of TLR in IBS patients according to the disease subtype. These results offer further support that microflora plays a central role in the complex pathophysiology of IBS providing novel pharmacological targets for this chronic gastrointestinal disorder according to bowel habits.  相似文献   
155.
The essential oils (EOs) of two populations of Azorella cryptantha (Clos) Reiche , a native species from San Juan Province, were obtained by hydrodistillation in a Clevenger‐type apparatus and characterized by GC‐FID and GC/MS analyses. The compounds identified amounted to 92.3 and 88.7% of the total oil composition for A. cryptantha from Bauchaceta (Ac‐BAU) and Agua Negra (Ac‐AN), respectively. The EO composition for the two populations was similar, although with differences in the identity and content of the main compounds and also in the identity of minor components. The main compounds of the Ac‐BAU EO were α‐pinene, α‐thujene, sabinene, δ‐cadinene, δ‐cadinol, transβ‐guaiene, and τ‐muurolol, while α‐pinene, α‐thujene, β‐pinene, γ‐cadinene, τ‐cadinol, δ‐cadinene, τ‐muurolol, and a not identified compound were the main constituents of the Ac‐AN EO, which also contained 3.0% of oxygenated monoterpenes. The repellent activity on Triatoma infestans nymphs was 100 and 92% for the Ac‐AN and Ac‐BAU EOs, respectively. Regarding the toxic effects on Ceratitis capitata, the EOs were very active with LD50 values lower than 11 μg/fly. The dermatophytes Microsporum gypseum, Trichophyton rubrum, and T. mentagrophytes and the bacterial strains Escherichia coli LM1, E. coli LM2, and Yersinia enterocolitica PI were more sensitive toward the Ac‐AN EO (MIC 125 μg/ml) than toward the Ac‐BAU EO. This is the first report on the composition of A. cryptantha EO and its anti‐insect and antimicrobial properties.  相似文献   
156.
In most metazoans mitochondria are inherited maternally. However, in some bivalve molluscs, two mitochondrial lineages are present: one transmitted through females (F-type), the other through males (M-type). This unique system is called Doubly Uniparental Inheritance (DUI) of mitochondria. In DUI species, M-type mitochondria have to invade the germ line of male embryos during development, otherwise sperm would transmit F-type mtDNA and DUI would fail. The mechanisms by which sperm mitochondria enter the germ line are still unknown. To address this question, we traced the movement of spermatozoon mitochondria (M-type) in embryos of the DUI species Ruditapes philippinarum by fertilizing eggs with sperm stained with the mitochondrial-specific vital dye MitoTracker Green. As in Mytilus DUI species, in R. philippinarum the distribution of sperm mitochondria follows two different patterns: an aggregated one in which these organelles locate near the first cleavage furrow, and a dispersed one in which sperm mitochondria are scattered. The presence of the two mitochondrial patterns in these taxa, together with their absence in species with Strictly Maternal Inheritance (SMI), confirms that their occurrence is related to DUI. Moreover, a Real-Time qPCR analysis showed that neither M-type nor F-type mitochondria undergo replication boosts in the earliest embryo development. This is the first study on sex-linked mtDNA copy number carried out by qPCR analysis on embryos of a DUI species and the first time the segregation patterns of sperm mitochondria are described in a DUI system other than Mytilus.  相似文献   
157.
Sara Benedetti  Pia Bernasconi  Enrico Bertini  Elena Biagini  Giuseppe Boriani  Cristina Capanni  Nicola Carboni  Giovanna Cenacchi  Marta Columbaro  Monica D’Adamo  Adele D’Amico  Maria Rosaria D’Apice  Marianna Fontana  Alessandra Gambineri  Giovanna Lattanzi  Rocco Liguori  Nadir M Maraldi  Laura Mazzanti  Eugenio Mercuri  Tiziana Mongini  Lucia O Morandi  Iria Neri  Giovanni Nigro  Giuseppe Novelli  Michela Ortolani  Renato Pasquali  Antonella Pini  Stefania Petrini  Luisa Politano  Stefano Previtali  Lisa Pucci  Claudio Rapezzi  Giulia Ricci  Carmelo Rodolico  Paolo Sbraccia  Emanuela Scarano  Gabriele Siciliano  Stefano Squarzoni  Antonio Toscano  Liliana Vercelli  Matteo Ziacchi 《Orphanet journal of rare diseases》2012,7(1):1-3
The need for a collaborative approach to complex inherited diseases collectively referred to as laminopathies, encouraged Italian researchers, geneticists, physicians and patients to join in the Italian Network for Laminopathies, in 2009. Here, we highlight the advantages and added value of such a multidisciplinary effort to understand pathogenesis, clinical aspects and try to find a cure for Emery-Dreifuss muscular dystrophy, Mandibuloacral dysplasia, Hutchinson-Gilford Progeria and forms of lamin-linked cardiomyopathy, neuropathy and lipodystrophy.  相似文献   
158.

Background

A modified laboratory-scale upflow anaerobic sludge blanket (UASB) reactor was used to obtain methane by treating hydrous ethanol vinasse. Vinasses or stillage are waste materials with high organic loads, and a complex composition resulting from the process of alcohol distillation. They must initially be treated with anaerobic processes due to their high organic loads. Vinasses can be considered multipurpose waste for energy recovery and once treated they can be used in agriculture without the risk of polluting soil, underground water or crops. In this sense, treatment of vinasse combines the elimination of organic waste with the formation of methane. Biogas is considered as a promising renewable energy source. The aim of this study was to determine the optimum organic loading rate for operating a modified UASB reactor to treat vinasse generated in the production of hydrous ethanol from sugar cane molasses.

Results

The study showed that chemical oxygen demand (COD) removal efficiency was 69% at an optimum organic loading rate (OLR) of 17.05 kg COD/m3-day, achieving a methane yield of 0.263 m3/kg CODadded and a biogas methane content of 84%. During this stage, effluent characterization presented lower values than the vinasse, except for potassium, sulfide and ammonia nitrogen. On the other hand, primers used to amplify the 16S-rDNA genes for the domains Archaea and Bacteria showed the presence of microorganisms which favor methane production at the optimum organic loading rate.

Conclusions

The modified UASB reactor proposed in this study provided a successful treatment of the vinasse obtained from hydrous ethanol production.Methanogen groups (Methanobacteriales and Methanosarcinales) detected by PCR during operational optimum OLR of the modified UASB reactor, favored methane production.
  相似文献   
159.
160.
Traditional methods for Chagas disease prevention are targeted at domestic vector reduction, as well as control of transfusion and maternal-fetal transmission. Population connectivity of Trypanosoma cruzi-infected vectors and hosts, among sylvatic, ecotone and domestic habitats could jeopardize targeted efforts to reduce human exposure. This connectivity was evaluated in a Mexican community with reports of high vector infestation, human infection, and Chagas disease, surrounded by agricultural and natural areas. We surveyed bats, rodents, and triatomines in dry and rainy seasons in three adjacent habitats (domestic, ecotone, sylvatic), and measured T. cruzi prevalence, and host feeding sources of triatomines. Of 12 bat and 7 rodent species, no bat tested positive for T. cruzi, but all rodent species tested positive in at least one season or habitat. Highest T. cruzi infection prevalence was found in the rodents, Baiomys musculus and Neotoma mexicana. In general, parasite prevalence was not related to habitat or season, although the sylvatic habitat had higher infection prevalence than by chance, during the dry season. Wild and domestic mammals were identified as bloodmeals of T. pallidipennis, with 9% of individuals having mixed human (4.8% single human) and other mammal species in bloodmeals, especially in the dry season; these vectors tested >50% positive for T. cruzi. Overall, ecological connectivity is broad across this matrix, based on high rodent community similarity, vector and T. cruzi presence. Cost-effective T. cruzi, vector control strategies and Chagas disease transmission prevention will need to consider continuous potential for parasite movement over the entire landscape. This study provides clear evidence that these strategies will need to include reservoir/host species in at least ecotones, in addition to domestic habitats.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号