全文获取类型
收费全文 | 2741篇 |
免费 | 235篇 |
专业分类
2976篇 |
出版年
2023年 | 27篇 |
2022年 | 55篇 |
2021年 | 80篇 |
2020年 | 51篇 |
2019年 | 81篇 |
2018年 | 96篇 |
2017年 | 101篇 |
2016年 | 105篇 |
2015年 | 166篇 |
2014年 | 157篇 |
2013年 | 194篇 |
2012年 | 273篇 |
2011年 | 220篇 |
2010年 | 144篇 |
2009年 | 113篇 |
2008年 | 146篇 |
2007年 | 127篇 |
2006年 | 113篇 |
2005年 | 106篇 |
2004年 | 107篇 |
2003年 | 90篇 |
2002年 | 89篇 |
2001年 | 41篇 |
2000年 | 24篇 |
1999年 | 14篇 |
1998年 | 18篇 |
1997年 | 10篇 |
1996年 | 10篇 |
1995年 | 12篇 |
1994年 | 10篇 |
1993年 | 21篇 |
1992年 | 17篇 |
1991年 | 14篇 |
1990年 | 11篇 |
1989年 | 16篇 |
1988年 | 9篇 |
1987年 | 5篇 |
1986年 | 8篇 |
1985年 | 8篇 |
1984年 | 5篇 |
1983年 | 5篇 |
1982年 | 7篇 |
1981年 | 6篇 |
1980年 | 6篇 |
1978年 | 4篇 |
1977年 | 6篇 |
1975年 | 7篇 |
1974年 | 7篇 |
1973年 | 9篇 |
1970年 | 4篇 |
排序方式: 共有2976条查询结果,搜索用时 0 毫秒
121.
Monteiro FA Sousa MM Cardoso I do Amaral JB Guimarães A Saraiva MJ 《Journal of neurochemistry》2006,97(1):151-161
Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disorder characterized by the extracellular deposition of transthyretin (TTR), especially in the PNS. Given the invasiveness of nerve biopsy, salivary glands (SG) from FAP patients were used previously in microarray analysis; mitogen-activated protein (MAP) kinase phosphatase 1 (MKP-1) was down-regulated in FAP. Results were validated by RT-PCR and immunohistochemistry both in SG and in nerve biopsies of different stages of disease progression. MKP-3 was also down-regulated in FAP SG biopsies. Given the relationship between MKPs and MAPKs, the latter were investigated. Only extracellular signal-regulated kinases 1/2 (ERK1/2) displayed increased activation in FAP SG and nerves. ERK1/2 kinase (MEK1/2) activation was also up-regulated in FAP nerves. In addition, an FAP transgenic mouse model revealed increased ERK1/2 activation in peripheral nerve affected with TTR deposition when compared to control animals. Cultured rat Schwannoma cell line treatment with TTR aggregates stimulated ERK1/2 activation, which was partially mediated by the receptor for advanced glycation end-products (RAGE). Moreover, caspase-3 activation triggered by TTR aggregates was abrogated by U0126, a MEK1/2 inhibitor, indicating that ERK1/2 activation is essential for TTR aggregates-induced cytotoxicity. Taken together, these data suggest that abnormally sustained activation of ERK in FAP may represent an early signaling cascade leading to neurodegeneration. 相似文献
122.
Altered ATP Hydrolysis Induced by Pentylenetetrazol Kindling in Rat Brain Synaptosomes 总被引:4,自引:0,他引:4
Bonan CD Amaral OB Rockenbach IC Walz R Battastini AM Izquierdo I Sarkis JJ 《Neurochemical research》2000,25(6):775-779
The ectonucleotidase pathway is an important metabolic source of extracellular adenosine. Adenosine has potent anticonvulsant effects on various models of epilepsy. One of these models is pentylenetetrazol (PTZ) kindling, in which repeated administration of subconvulsive doses of this drug induces progressive intensification of seizure activity. In this study, we examine the effect of a single convulsive injection (60 mg/kg, i.p.) or 10 successive (35 mg/kg, i.p.) injections of PTZ on synaptosomal ectonucleotidases. Our results have shown that no changes in ectonucleotidase activities were seen at 0, 1, and 24 h or at 5 days after a single convulsive PTZ injection. However, after PTZ-kindling, rats which were more resistant to seizure development presented an increase in ATP hydrolysis in synaptosomes from hippocampus and cerebral cortex (44% and 28%, respectively). These results suggest that changes in nucleotide hydrolysis may represent an important mechanism in the modulation of chronic epileptic activity in this model. 相似文献
123.
Joseph A. Lewnard Lara Jirmanus Nivison Nery Júnior Paulo R. Machado Marshall J. Glesby Albert I. Ko Edgar M. Carvalho Albert Schriefer Daniel M. Weinberger 《PLoS neglected tropical diseases》2014,8(10)
Introduction
Cutaneous leishmaniasis (CL) is a vector-borne disease of increasing importance in northeastern Brazil. It is known that sandflies, which spread the causative parasites, have weather-dependent population dynamics. Routinely-gathered weather data may be useful for anticipating disease risk and planning interventions.Methodology/Principal Findings
We fit time series models using meteorological covariates to predict CL cases in a rural region of Bahía, Brazil from 1994 to 2004. We used the models to forecast CL cases for the period 2005 to 2008. Models accounting for meteorological predictors reduced mean squared error in one, two, and three month-ahead forecasts by up to 16% relative to forecasts from a null model accounting only for temporal autocorrelation.Significance
These outcomes suggest CL risk in northeastern Brazil might be partially dependent on weather. Responses to forecasted CL epidemics may include bolstering clinical capacity and disease surveillance in at-risk areas. Ecological mechanisms by which weather influences CL risk merit future research attention as public health intervention targets. 相似文献124.
The Revised Classification of Eukaryotes 总被引:1,自引:0,他引:1
Sina M. Adl Alastair G. B. Simpson Christopher E. Lane Julius Lukeš David Bass Samuel S. Bowser Matthew W. Brown Fabien Burki Micah Dunthorn Vladimir Hampl Aaron Heiss Mona Hoppenrath Enrique Lara Line le Gall Denis H. Lynn Hilary McManus Edward A. D. Mitchell Sharon E. Mozley‐Stanridge Laura W. Parfrey Jan Pawlowski Sonja Rueckert Laura Shadwick Conrad L. Schoch Alexey Smirnov Frederick W. Spiegel 《The Journal of eukaryotic microbiology》2012,59(5):429-514
This revision of the classification of eukaryotes, which updates that of Adl et al. [J. Eukaryot. Microbiol. 52 (2005) 399], retains an emphasis on the protists and incorporates changes since 2005 that have resolved nodes and branches in phylogenetic trees. Whereas the previous revision was successful in re‐introducing name stability to the classification, this revision provides a classification for lineages that were then still unresolved. The supergroups have withstood phylogenetic hypothesis testing with some modifications, but despite some progress, problematic nodes at the base of the eukaryotic tree still remain to be statistically resolved. Looking forward, subsequent transformations to our understanding of the diversity of life will be from the discovery of novel lineages in previously under‐sampled areas and from environmental genomic information. 相似文献
125.
Lara Saraiva Alanna Silva Reis Jeronimo Marteleto Nunes Rugani Agnes Ant?nia Sampaio Pereira Felipe Dutra Rêgo Ana Cristina Vianna Mariano da Rocha Lima Célia Maria Ferreira Gontijo José Dilermando Andrade Filho 《PloS one》2015,10(8)
Brazil is one of the most important endemic areas for leishmaniasis worldwide. Protected areas that are tourist attractions likely present an important risk of transmission of cutaneous leishmaniasis (CL). Furthermore, with the geographical expansion of visceral leishmaniasis (VL), several studies have recorded the occurrence of its vector, Lutzomyia longipalpis, and cases of human and canine VL in such tourist areas. The Parque Estadual do Sumidouro is an environmentally protected area located in the Brazilian Cerrado biome and in an important area endemic for leishmaniasis in the state of Minas Gerais. The purpose of this study was to monitor the sand fly fauna in areas of tourist activity in the park. Sampling was performed every month, from September 2011 to August 2013, using CDC light traps at six sites of differing environmental characteristics. Sampled specimens were identified following Galati (2003), and females were submitted to molecular techniques for the detection and identification of Leishmania DNA. A total of 4,675 sand fly specimens of 25 species belonging to nine genera were collected. The most abundant species were Micropygomyia quinquefer, Lutzomyia renei and Pintomyia pessoai, although only Pi. pessoai is implicated in the transmission of Leishmania braziliensis. The species accumulation curve reached saturation on the 16th sampling event. Species richness, diversity and evenness differed among the sampled areas. The seasonal curve was not determined by a single unique species, and no single species was the most abundant in all environments sampled. The main vector of Leishmania (Leishmania) infantum, Lutzomyia longipalpis, accounted for only 5.35% of the specimens collected. Proven or suspected vectors of Leishmania (Viannia) braziliensis were recorded, and one female of the cortellezzii complex tested positive for Le. braziliensis DNA. Even with a low infection rate (0.62%), these data indicate the circulation of the parasite and reinforce the need for entomological and epidemiological surveillance in the park and its surroundings. 相似文献
126.
Nontyphoid salmonellosis caused by Salmonella enterica is the most common bacterial food-borne illness in humans, and fresh produce, including tomatoes, is a common vehicle. Accumulating data indicate that human enteric pathogenic bacteria, including S. enterica, interact actively with plants. Tomato plants were inoculated with S. enterica to evaluate plausible contamination routes and to determine if the tomato cultivar affects S. enterica colonization. S. enterica population levels on tomato leaves were cultivar dependent. S. enterica levels on Solanum pimpinellifolium (West Virginia 700 [WVa700]) were lower than on S. lycopersicum cultivars. S. enterica preferentially colonized type 1 trichomes and rarely interacted with stomata, unlike what has been reported for cut lettuce leaves. Early S. enterica leaf colonization led to contamination of all fruit, with levels as high as 10(5) CFU per fruit. Reduced bacterial speck lesion formation correlated with reduced S. enterica populations in the phyllosphere. Tomato pedicels and calyxes also harbored large S. enterica populations following inoculation via contaminated water postharvest. WVa700 green fruit harbored significantly smaller S. enterica populations than did red fruit or S. lycopersicum fruit. We found that plants irrigated with contaminated water had larger S. enterica populations than plants grown from seeds planted in infested soil. However, both routes of contamination resulted in detectable S. enterica populations in the phyllosphere. Phyllosphere S. enterica populations pose a risk of fruit contamination and subsequent human disease. Restricting S. enterica phyllosphere populations may result in reduced fruit contamination. We have identified WVa700 as a tomato cultivar that can restrict S. enterica survival in the phyllosphere. 相似文献
127.
Virulence markers associated with Trueperella pyogenes infections in livestock and companion animals 下载免费PDF全文
128.
129.
Analysis of the composition of bacterial communities in oil reservoirs from a southern offshore Brazilian basin 总被引:2,自引:0,他引:2
Sette LD Simioni KC Vasconcellos SP Dussan LJ Neto EV Oliveira VM 《Antonie van Leeuwenhoek》2007,91(3):253-266
The aim of this study was to characterize and compare the bacterial community structure of two distinct oil samples from a
petroleum field in Brazil by using both molecular, based on the construction of 16S rRNA gene libraries, and cultivation methods.
Statistical comparisons of libraries based on Amplified Ribosomal DNA Restriction Analysis (ARDRA) data revealed no significant
differences between the communities recovered in the non-biodegraded (NBD) and highly biodegraded oils (HBD). BlastN analysis
of the 16S rRNA gene sequences representative of distinct ribotypes from both oils showed the presence of nine different bacterial
genera in these samples, encompassing members of the genera Arcobacter, Halanaerobium, Marinobacter, Propionibacterium, Streptomyces, Leuconostoc, Acinetobacter, Bacillus and Streptococcus. Enrichments obtained using oil as inoculum and sole carbon source yielded bacterial isolates showing high 16S rRNA gene
sequence similarity with Achromobacter xylosoxidans, Bacillus subtilis, Brevibacillus sp., Dietzia sp. and Methylobacterium sp. Comparison between the data obtained using cultivation-independent and enrichment cultures suggests that different selection
of community members may occur when using distinct approaches. All the organisms found, except for Leuconostoc sp. and Streptococus sp., have been previously reported in the literature as hydrocarbon degraders and/or associated to oil field environments. 相似文献
130.