全文获取类型
收费全文 | 205篇 |
免费 | 7篇 |
出版年
2023年 | 2篇 |
2022年 | 6篇 |
2021年 | 10篇 |
2020年 | 7篇 |
2019年 | 5篇 |
2018年 | 5篇 |
2017年 | 9篇 |
2016年 | 5篇 |
2015年 | 12篇 |
2014年 | 8篇 |
2013年 | 21篇 |
2012年 | 16篇 |
2011年 | 12篇 |
2010年 | 6篇 |
2009年 | 9篇 |
2008年 | 19篇 |
2007年 | 8篇 |
2006年 | 11篇 |
2005年 | 4篇 |
2004年 | 6篇 |
2003年 | 3篇 |
2002年 | 8篇 |
2001年 | 4篇 |
1999年 | 2篇 |
1997年 | 1篇 |
1991年 | 1篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1984年 | 2篇 |
1978年 | 1篇 |
1976年 | 4篇 |
1975年 | 1篇 |
排序方式: 共有212条查询结果,搜索用时 15 毫秒
141.
142.
Jennifer K. Frediani Dean P. Jones Nestan Tukvadze Karan Uppal Eka Sanikidze Maia Kipiani ViLinh T. Tran Gautam Hebbar Douglas I. Walker Russell R. Kempker Shaheen S. Kurani Romain A. Colas Jesmond Dalli Vin Tangpricha Charles N. Serhan Henry M. Blumberg Thomas R. Ziegler 《PloS one》2014,9(10)
We aimed to characterize metabolites during tuberculosis (TB) disease and identify new pathophysiologic pathways involved in infection as well as biomarkers of TB onset, progression and resolution. Such data may inform development of new anti-tuberculosis drugs. Plasma samples from adults with newly diagnosed pulmonary TB disease and their matched, asymptomatic, sputum culture-negative household contacts were analyzed using liquid chromatography high-resolution mass spectrometry (LC-MS) to identify metabolites. Statistical and bioinformatics methods were used to select accurate mass/charge (m/z) ions that were significantly different between the two groups at a false discovery rate (FDR) of q<0.05. Two-way hierarchical cluster analysis (HCA) was used to identify clusters of ions contributing to separation of cases and controls, and metabolomics databases were used to match these ions to known metabolites. Identity of specific D-series resolvins, glutamate and Mycobacterium tuberculosis (Mtb)-derived trehalose-6-mycolate was confirmed using LC-MS/MS analysis. Over 23,000 metabolites were detected in untargeted metabolomic analysis and 61 metabolites were significantly different between the two groups. HCA revealed 8 metabolite clusters containing metabolites largely upregulated in patients with TB disease, including anti-TB drugs, glutamate, choline derivatives, Mycobacterium tuberculosis-derived cell wall glycolipids (trehalose-6-mycolate and phosphatidylinositol) and pro-resolving lipid mediators of inflammation, known to stimulate resolution, efferocytosis and microbial killing. The resolvins were confirmed to be RvD1, aspirin-triggered RvD1, and RvD2. This study shows that high-resolution metabolomic analysis can differentiate patients with active TB disease from their asymptomatic household contacts. Specific metabolites upregulated in the plasma of patients with active TB disease, including Mtb-derived glycolipids and resolvins, have potential as biomarkers and may reveal pathways involved in TB disease pathogenesis and resolution. 相似文献
143.
Binema mirzaia (Basir, 1942a) Basir, 1956, Cameronia nisari (Parveen and Jairajpuri, 1985) Adamson and Van Waerebeke, 1992a and
Mirzaiella meerutensis Singh and Malti, 2003 are redescribed morphologically along with molecular identification from the intestine
of mole cricket Gryllotalpa africana. Molecular characterization was carried out using the D2–D3 expansion domains of the 18S
ribosomal DNA region. This study first time presents molecular data for the above three nematode species. 相似文献
144.
The present study describes the molecular phylogenetic analysis of Dactylogyroides longicirrus (Monogenea: Dactylogyridae)
infecting the gill filaments of fish Puntius sophore from the site Guwahati, Assam, India. The parasite Dactylogyroides longicirrus
(Tripathi, 1959) Gusev, 1976 from Northeast Indian region is presented based on sequence data of a 738 base-pair fragment of
ribosomal 18S small subunit and first internal transcribed spacer (ITS 1). Phylogenetic relationships were inferred using neighbour
joning and maximum parsimony methods and the results support the validation of D. longicirrus. The study is also supported by
secondary structure model prediction by using minimum free energy which can be considered a promising tool for monogenean
species identification. This is the first report of this parasite from Northeast region of India, with this, the 18S and ITS 1 rDNA
region amplified in the study is also the first sequence of the genus Dactylogyroides. 相似文献
145.
Gajanand Sharma Richa Sharma Meenakshi Sharma Anshu Dandia Preeti Bansal 《Russian Journal of Bioorganic Chemistry》2013,39(3):318-328
An environmentally benign solvent free synthesis of various spiro-1,4-dihydropyridines (1,4-DHPs) incorporating 2-oxindole/piperidines is performed in 5–8 min with reasonable purity in 80–90% yield under microwave irradiation using montmorillonite KSF as an inorganic solid support. The reaction is found to be general with respect to various cyclic carbonyl compounds, e.g. cyclohexanone, substituted indole-2,3-dione, and piperidinone derivatives. In our study, these compounds were also found effective against dermatophytes and other fungal organisms. Our results suggest that novel spiro derivatives can be used for the treatment of dermatophytosis or ringworm infections. 相似文献
146.
Anshu Chen Shixin Sun RangaswamyRao Ravikumar Nishant P. Visavadiya Joe E. Springer 《Neurochemical research》2013,38(11):2247-2255
In this experimental study, differential labeling with isobaric tags for relative and absolute quantitation (iTRAQ) reagents followed by liquid chromatography (LC) and tandem mass spectrometry (MS/MS) proteomic approach was used to investigate differences in the proteome of rat spinal cord at 24 h following a moderate contusion injury. Spinal cord protein samples from the injury epicenter (or from sham controls) were trypsinized and differentially labeled with iTRAQ isotopic reagents. The differentially labeled samples were then combined into one sample mixture, separated by LC, and analyzed using MS/MS. Proteins were quantified by comparing the peak areas of iTRAQ reporter fragment ions in MS/MS spectra. The outcome of this analysis revealed that proteins involved in ubiquitination, endocytosis and exocytosis, energy metabolism, inflammatory response, oxidative stress, cytoskeletal disruption, and vascular damage were significantly altered at 24 h following spinal cord injury (SCI). This study demonstrates the utility of the iTRAQ method in proteomic studies and provides further insights into secondary events that occur during acute times following SCI. 相似文献
147.
Ira Jain Jessica L. Danger Cameron Burgess Timsy Uppal Paul Sumby 《Molecular microbiology》2020,113(1):190-207
The group A Streptococcus (GAS) causes diseases that range from mild (e.g. pharyngitis) to severely invasive (e.g. necrotizing fasciitis). Strain- and serotype-specific differences influence the ability of isolates to cause individual diseases. At the center of this variability is the CovR/S two-component system and the accessory protein RocA. Through incompletely defined mechanisms, CovR/S and RocA repress the expression of more than a dozen immunomodulatory virulence factors. Alleviation of this repression is selected for during invasive infections, leading to the recovery of covR, covS or rocA mutant strains. Here, we investigated how RocA promotes CovR/S activity, identifying that RocA is a pseudokinase that interacts with CovS. Disruption of CovS kinase or phosphatase activities abolishes RocA function, consistent with RocA acting through the modulation of CovS activity. We also identified, in conflict with a previous study, that the RocA regulon includes the secreted protease-encoding gene speB. Finally, we discovered an inverse correlation between the virulence of wild-type, rocA mutant, covS mutant and covR mutant strains during invasive infection and their fitness in an ex vivo upper respiratory tract model. Our data inform on mechanisms that control GAS disease potential and provide an explanation for observed strain- and serotype-specific variability in RocA function. 相似文献
148.
Rukmini Mukherjee Anshu Bhattacharya Denisa Bojkova Ahmad Reza Mehdipour Donghyuk Shin Khadija Shahed Khan Hayley Hei-Yin Cheung Kam-Bo Wong Wai-Lung Ng Jindrich Cinatl Paul P. Geurink Gerbrand J. van der Heden van Noort Krishnaraj Rajalingam Sandra Ciesek Gerhard Hummer Ivan Dikic 《The Journal of biological chemistry》2021,297(2)
Apart from prevention using vaccinations, the management options for COVID-19 remain limited. In retrospective cohort studies, use of famotidine, a specific oral H2 receptor antagonist (antihistamine), has been associated with reduced risk of intubation and death in patients hospitalized with COVID-19. In a case series, nonhospitalized patients with COVID-19 experienced rapid symptom resolution after taking famotidine, but the molecular basis of these observations remains elusive. Here we show using biochemical, cellular, and functional assays that famotidine has no effect on viral replication or viral protease activity. However, famotidine can affect histamine-induced signaling processes in infected Caco2 cells. Specifically, famotidine treatment inhibits histamine-induced expression of Toll-like receptor 3 (TLR3) in SARS-CoV-2 infected cells and can reduce TLR3-dependent signaling processes that culminate in activation of IRF3 and the NF-κB pathway, subsequently controlling antiviral and inflammatory responses. SARS-CoV-2-infected cells treated with famotidine demonstrate reduced expression levels of the inflammatory mediators CCL-2 and IL6, drivers of the cytokine release syndrome that precipitates poor outcome for patients with COVID-19. Given that pharmacokinetic studies indicate that famotidine can reach concentrations in blood that suffice to antagonize histamine H2 receptors expressed in mast cells, neutrophils, and eosinophils, these observations explain how famotidine may contribute to the reduced histamine-induced inflammation and cytokine release, thereby improving the outcome for patients with COVID-19. 相似文献
149.
A solvent tolerant isolate of Enterobacter aerogenes 总被引:2,自引:0,他引:2
A solvent tolerant strain of Enterobacter aerogenes was isolated from soil by cyclohexane enrichment. Presence of cyclohexane (20%) in culture media prolonged the lag phase and caused reduction in biomass. Transmission electron micrographs showed convoluted cell membrane and accumulation of solvent in case of the cells grown in cyclohexane. The Enterobacter isolate was able to grow in the range of organic solvents having log P above 3.2 and also in presence of mercury, thus showing potential for treatment of solvent rich wastes. 相似文献
150.
Olaharski A Albertini S Kirchner S Platz S Uppal H Lin H Kolaja K 《Mutation research》2009,672(1):10-16
The GreenScreen GADD45alpha indicator assay has been assessed for its concordance with in vitro genotoxicity and rodent carcinogenicity bioassay data. To test robustness, sensitivity, and specificity of the assay, 91 compounds with known genotoxicity results were screened in a blinded manner. Fifty seven of the compounds were classified as in vitro genotoxic whereas 34 were non-genotoxic. Out of the 91 compounds, 50 had been tested in 2-year carcinogenicity assays, with 33 identified to be rodent carcinogens and 17 non-carcinogens. Gadd45alpha assay sensitivity and specificity for genotoxicity was 30% and 97%, respectively (17/57 and 33/34), whereas its sensitivity and specificity for rodent carcinogenicity was 30% and 88%, respectively (10/33 and 15/17). Gadd45alpha assay genotoxicity results from this validation study exhibited a high concordance with previously published results as well as for compound test results generated at two different sites (91%, 19/21), indicating that the assay is both robust and reproducible. In conclusion, results from this blinded and independent validation study indicate that the GreenScreen GADD45 indicator assay is reproducible and reliable with low sensitivity and high specificity for identifying genotoxic and carcinogenic compounds. 相似文献