全文获取类型
收费全文 | 668篇 |
免费 | 46篇 |
出版年
2023年 | 9篇 |
2022年 | 20篇 |
2021年 | 24篇 |
2020年 | 22篇 |
2019年 | 13篇 |
2018年 | 20篇 |
2017年 | 22篇 |
2016年 | 30篇 |
2015年 | 45篇 |
2014年 | 46篇 |
2013年 | 40篇 |
2012年 | 54篇 |
2011年 | 48篇 |
2010年 | 30篇 |
2009年 | 25篇 |
2008年 | 35篇 |
2007年 | 33篇 |
2006年 | 29篇 |
2005年 | 28篇 |
2004年 | 22篇 |
2003年 | 18篇 |
2002年 | 18篇 |
2001年 | 2篇 |
2000年 | 5篇 |
1999年 | 4篇 |
1998年 | 6篇 |
1997年 | 4篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1993年 | 3篇 |
1987年 | 3篇 |
1984年 | 1篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 7篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1976年 | 3篇 |
1975年 | 1篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1971年 | 2篇 |
1970年 | 3篇 |
1969年 | 3篇 |
1967年 | 2篇 |
1966年 | 1篇 |
1964年 | 3篇 |
1925年 | 1篇 |
排序方式: 共有714条查询结果,搜索用时 250 毫秒
41.
Daniele Gabriel-Costa Telma Fatima da Cunha Luiz Roberto Grassmann Bechara Rodrigo Soares Fortunato Luiz Henrique Marchesi Bozi Marcele de Almeida Coelho Maria Luiza Barreto-Chaves Patricia Chakur Brum 《PloS one》2015,10(5)
Background
Besides its role as a fuel source in intermediary metabolism, lactate has been considered a signaling molecule modulating lactate-sensitive genes involved in the regulation of skeletal muscle metabolism. Even though the flux of lactate is significantly high in the heart, its role on regulation of cardiac genes regulating lactate oxidation has not been clarified yet. We tested the hypothesis that lactate would increase cardiac levels of reactive oxygen species and up-regulate the expression of genes related to lactate oxidation complex.Methods/Principal Findings
Isolated hearts from male adult Wistar rats were perfused with control, lactate or acetate (20mM) added Krebs-Henseleit solution during 120 min in modified Langendorff apparatus. Reactive oxygen species (O2 ●-/H2O2) levels, and NADH and NADPH oxidase activities (in enriched microsomal or plasmatic membranes, respectively) were evaluated by fluorimetry while SOD and catalase activities were evaluated by spectrophotometry. mRNA levels of lactate oxidation complex and energetic enzymes MCT1, MCT4, HK, LDH, PDH, CS, PGC1α and COXIV were quantified by real time RT-PCR. Mitochondrial DNA levels were also evaluated. Hemodynamic parameters were acquired during the experiment. The key findings of this work were that lactate elevated cardiac NADH oxidase activity but not NADPH activity. This response was associated with increased cardiac O2 ●-/H2O2 levels and up-regulation of MCT1, MCT4, LDH and PGC1α with no changes in HK, PDH, CS, COXIV mRNA levels and mitochondrial DNA levels. Lactate increased NRF-2 nuclear expression and SOD activity probably as counter-regulatory responses to increased O2 ●-/H2O2.Conclusions
Our results provide evidence for lactate-induced up-regulation of lactate oxidation complex associated with increased NADH oxidase activity and cardiac O2 ●-/H2O2 driving to an anti-oxidant response. These results unveil lactate as an important signaling molecule regulating components of the lactate oxidation complex in cardiac muscle. 相似文献42.
Luiza Helena Urso Pitassi Pedro Paulo Vissotto de Paiva Diniz Diana Gerardi Scorpio Marina Rovani Drummond Bruno Grosselli Lania Maria Lourdes Barjas-Castro Rovilson Gilioli Silvia Colombo Stanley Sowy Edward B. Breitschwerdt William L. Nicholson Paulo Eduardo Neves Ferreira Velho 《PLoS neglected tropical diseases》2015,9(1)
Bartonella species are blood-borne, re-emerging organisms, capable of causing prolonged infection with diverse disease manifestations, from asymptomatic bacteremia to chronic debilitating disease and death. This pathogen can survive for over a month in stored blood. However, its prevalence among blood donors is unknown, and screening of blood supplies for this pathogen is not routinely performed. We investigated Bartonella spp. prevalence in 500 blood donors from Campinas, Brazil, based on a cross-sectional design. Blood samples were inoculated into an enrichment liquid growth medium and sub-inoculated onto blood agar. Liquid culture samples and Gram-negative isolates were tested using a genus specific ITS PCR with amplicons sequenced for species identification. Bartonella henselae and Bartonella quintana antibodies were assayed by indirect immunofluorescence. B. henselae was isolated from six donors (1.2%). Sixteen donors (3.2%) were Bartonella-PCR positive after culture in liquid or on solid media, with 15 donors infected with B. henselae and one donor infected with Bartonella clarridgeiae. Antibodies against B. henselae or B. quintana were found in 16% and 32% of 500 blood donors, respectively. Serology was not associated with infection, with only three of 16 Bartonella-infected subjects seropositive for B. henselae or B. quintana. Bartonella DNA was present in the bloodstream of approximately one out of 30 donors from a major blood bank in South America. Negative serology does not rule out Bartonella spp. infection in healthy subjects. Using a combination of liquid and solid cultures, PCR, and DNA sequencing, this study documents for the first time that Bartonella spp. bacteremia occurs in asymptomatic blood donors. Our findings support further evaluation of Bartonella spp. transmission which can occur through blood transfusions. 相似文献
43.
44.
Over the past decades, genetic analyses performed in vertebrate and invertebrate organisms deciphered numerous cellular and molecular mechanisms deployed during sexual development and identified genetic circuitries largely shared among bilaterians. In contrast, the functional analysis of the mechanisms that support regenerative processes in species randomly scattered among the animal kingdom, were limited by the lack of genetic tools. Consequently, unifying principles explaining how stress and injury can lead to the reactivation of a complete developmental program with restoration of original shape and function remained beyond reach of understanding. Recent data on cell plasticity suggest that beside the classical developmental approach, the analysis of homeostasis and asexual reproduction in adult organisms provides novel entry points to dissect the regenerative potential of a given species, a given organ or a given tissue. As a clue, both tissue homeostasis and regeneration dynamics rely on the availability of stem cells and/or on the plasticity of differentiated cells to replenish the missing structure. The freshwater Hydra polyp provides us with a unique model system to study the intricate relationships between the mechanisms that regulate the maintenance of homeostasis, even in extreme conditions (starvation and overfeeding) and the reactivation of developmental programs after bisection or during budding. Interestingly head regeneration in Hydra can follow several routes according to the level of amputation, suggesting that indeed the homeostatic background dramatically influences the route taken to bridge injury and regeneration. Mol. Reprod. Dev. 77:837–855, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
45.
Luciana Tovo‐Rodrigues Sidia M. Callegari‐Jacques M. Luiza Petzl‐Erler Luiza Tsuneto Francisco M. Salzano Mara H. Hutz 《American journal of physical anthropology》2010,143(3):458-464
The DRD4 variable number of tandem repeats (VNTR) allele distribution of 172 Guarani (Kaiowá and Ñandeva subgroups) and Kaingang Brazilian Amerindians is reported. These results are integrated with those previously obtained for this ethnic group. Allele frequencies for the three populations are within the interval observed for 15 other Native American populations and show intermediate values between those observed in Amazonia and Patagonia. Significant differences in allele distribution between recent past hunter–gatherer and agriculturalist populations are observed, with an increase of the 7R allele among hunter–gatherers (P < 0.001). Analysis of molecular variance (AMOVA) and pairwise FST data suggest three distinct sectors for the genetic landscape of Native South America: Andes, Center/Southeast region, and Amazonia. Common traits among hunter–gatherers such as novelty‐seeking temperament, hyperactivity, and impulsivity could have been important and advantageous in new environments during America's prehistoric colonization. Am J Phys Anthropol, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
46.
Joana Tomomi Sumikawa Marlon Vilela de Brito Maria Ligia Rodrigues Macedo Adriana F. Uchoa Antonio Miranda Ana Paula U. Araujo Rosemeire A. Silva-Lucca Misako Uemura Sampaio Maria Luiza Vilela Oliva 《Phytochemistry》2010,71(2-3):214-220
Three plant proteinase inhibitors BbKI (kallikrein inhibitor) and BbCI (cruzipain inhibitor) from Bauhinia bauhinioides, and a BrTI (trypsin inhibitor) from B. rufa, were examined for other effects in Callosobruchus maculatus development; of these only BrTI affected bruchid emergence. BrTI and BbKI share 81% identities in their primary sequences and the major differences between them are the regions comprising the RGD and RGE motifs in BrTI. These sequences were shown to be essential for BrTI insecticidal activity, since a modified BbKI [that is a recombinant form (BbKIm) with some amino acid residues replaced by those found in BrTI sequence] also strongly inhibited insect development. By using synthetic peptides related to the BrTI sequence, YLEAPVARGDGGLA-NH2 (RGE) and IVYYPDRGETGL-NH2 (RGE), it was found that the peptide with an RGE sequence was able to block normal development of C. maculatus larvae (ED50 0.16% and LD50 0.09%), this being even more effective than the native protein. 相似文献
47.
Forms of the protozoan of the Hepatozoon genus are detected free in the circulation and also within some of the erythrocytes of infected snakes. In healthy snakes, DNA fragmentation and cell death usually affect a few circulating erythrocytes in agreement with the long life span expected for these cells. In the present study we investigated whether infection by Hepatozoon spp. affected the incidence of DNA fragmentation and cell death in erythrocytes from the rattlesnake, Crotalus durissus terrificus. Methods such as the kinetics of Feulgen-DNA hydrolysis, and the TUNEL and comet assays, previously used for the study of chromatin organization and DNA fragmentation in erythrocytes of healthy snakes, were used. The results indicated that Hepatozoon spp. increased the DNA fragmentation and chromatin condensation typical of cell death in circulating erythrocytes of C. d. terrificus, including cells that do not harbour the parasite. The Hepatozoon infection is thus suggested to accelerate destruction of erythrocytes in the rattlesnake, not only affecting cells harbouring the parasite, but also in those without it. 相似文献
48.
INTRODUCTION: In order to be effective, treatment for osteoporosis must be long-term. Unfortunately, according to clinical trials and clinical practice the most frequent cause of patient resignation from the treatment is adverse reactions to the medications. In the case of bisphosphonates they are most frequently connected with irritant impact of the drug on gastrointestinal mucosa. The aim of our study was to answer the question whether alendronate tablets coated with a thin neutral layer may protect gastrointestinal mucosa from the irritant effects of the active substance. MATERIAL AND METHODS: Three types of tablets were administered into the cheek pouches of 18 Syrian hamsters (divided into 3 experimental groups: I, II, III) i.e. regular alendronate tablets, coated alendronate tablets and placebo. The tablets were applied for 4 minutes a day on 4 consecutive days. 24 hours after the last application, the animals were sacrificed and segments of buccal tissue were taken for histopathological examination. Oral tissue reaction was assessed using the microscopic examination grading system developed by ISO. The following adverse changes of the tissue were recorded: epithelial lesions, leucocyte infiltration, vascular congestion and oedema. Later the irritation index was calculated. RESULTS: The irritation index was 11.0 (moderately irritant), 0.0 and 0.0 (none-irritant), in each group respectively. CONCLUSION: It appears that the administration of the coated alendronate tablets reduces the frequency and intensity of the local adverse events from the gastrointestinal tract. 相似文献
49.
Oliveira Willams Silva Jéssica Luiza S. Cruz-Neto Oswaldo Oliveira Marcela Tomaz P. Fernandes de Albuquerque Isabelle Borges Laís Angélica Lopes Ariadna Valentina 《Journal of plant research》2022,135(2):235-245
Journal of Plant Research - In mixed-ploidy populations, newly formed polyploids initially occur at low frequencies when compared to diploids. However, polyploidy may lead to morphological and... 相似文献
50.
Dorota?Gurda Luiza?Handschuh Weronika?Kotkowiak Hieronim?JakubowskiEmail author 《Amino acids》2015,47(7):1319-1339
Genetic or nutritional deficiencies in homocysteine (Hcy) metabolism lead to hyperhomocysteinemia (HHcy) and cause endothelial dysfunction, a hallmark of atherosclerosis. In addition to Hcy, related metabolites accumulate in HHcy but their role in endothelial dysfunction is unknown. Here, we examine how Hcy-thiolactone, N-Hcy-protein, and Hcy affect gene expression and molecular pathways in human umbilical vein endothelial cells. We used microarray technology, real-time quantitative polymerase chain reaction, and bioinformatic analysis with PANTHER, DAVID, and Ingenuity Pathway Analysis (IPA) resources. We identified 47, 113, and 30 mRNAs regulated by N-Hcy-protein, Hcy-thiolactone, and Hcy, respectively, and found that each metabolite induced a unique pattern of gene expression. Top molecular pathways affected by Hcy-thiolactone were chromatin organization, one-carbon metabolism, and lipid-related processes [?log(P value) = 20–31]. Top pathways affected by N-Hcy-protein and Hcy were blood coagulation, sulfur amino acid metabolism, and lipid metabolism [?log(P value)] = 4–11; also affected by Hcy-thiolactone, [?log(P value) = 8–14]. Top disease related to Hcy-thiolactone, N-Hcy-protein, and Hcy was ‘atherosclerosis, coronary heart disease’ [?log(P value) = 9–16]. Top-scored biological networks affected by Hcy-thiolactone (score = 34–40) were cardiovascular disease and function; those affected by N-Hcy-protein (score = 24–35) were ‘small molecule biochemistry, neurological disease,’ and ‘cardiovascular system development and function’; and those affected by Hcy (score = 25–37) were ‘amino acid metabolism, lipid metabolism,’ ‘cellular movement, and cardiovascular and nervous system development and function.’ These results indicate that each Hcy metabolite uniquely modulates gene expression in pathways important for vascular homeostasis and identify new genes and pathways that are linked to HHcy-induced endothelial dysfunction and vascular disease. 相似文献