全文获取类型
收费全文 | 313篇 |
免费 | 19篇 |
国内免费 | 1篇 |
出版年
2023年 | 2篇 |
2022年 | 1篇 |
2021年 | 11篇 |
2020年 | 3篇 |
2019年 | 7篇 |
2018年 | 9篇 |
2017年 | 5篇 |
2016年 | 14篇 |
2015年 | 20篇 |
2014年 | 15篇 |
2013年 | 18篇 |
2012年 | 38篇 |
2011年 | 28篇 |
2010年 | 16篇 |
2009年 | 12篇 |
2008年 | 12篇 |
2007年 | 19篇 |
2006年 | 14篇 |
2005年 | 23篇 |
2004年 | 19篇 |
2003年 | 6篇 |
2002年 | 7篇 |
2001年 | 5篇 |
2000年 | 5篇 |
1999年 | 5篇 |
1998年 | 3篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1986年 | 1篇 |
1984年 | 2篇 |
1983年 | 1篇 |
排序方式: 共有333条查询结果,搜索用时 109 毫秒
41.
Do TQ Moshkani S Castillo P Anunta S Pogosyan A Cheung A Marbois B Faull KF Ernst W Chiang SM Fujii G Clarke CF Foster K Porter E 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(6):4177-4187
Mucosal surfaces provide first-line defense against microbial invasion through their complex secretions. The antimicrobial activities of proteins in these secretions have been well delineated, but the contributions of lipids to mucosal defense have not been defined. We found that normal human nasal fluid contains all major lipid classes (in micrograms per milliliter), as well as lipoproteins and apolipoprotein A-I. The predominant less polar lipids were myristic, palmitic, palmitoleic, stearic, oleic, and linoleic acid, cholesterol, and cholesteryl palmitate, cholesteryl linoleate, and cholesteryl arachidonate. Normal human bronchioepithelial cell secretions exhibited a similar lipid composition. Removal of less-polar lipids significantly decreased the inherent antibacterial activity of nasal fluid against Pseudomonas aeruginosa, which was in part restored after replenishing the lipids. Furthermore, lipids extracted from nasal fluid exerted direct antibacterial activity in synergism with the antimicrobial human neutrophil peptide HNP-2 and liposomal formulations of cholesteryl linoleate and cholesteryl arachidonate were active against P. aeruginosa at physiological concentrations as found in nasal fluid and exerted inhibitory activity against other Gram-negative and Gram-positive bacteria. These data suggest that host-derived lipids contribute to mucosal defense. The emerging concept of host-derived antimicrobial lipids unveils novel roads to a better understanding of the immunology of infectious diseases. 相似文献
42.
Le MT Wertheim HF Nguyen HD Taylor W Hoang PV Vuong CD Nguyen HL Nguyen HH Nguyen TQ Nguyen TV Van TD Ngoc BT Bui TN Nguyen BG Nguyen LT Luong ST Phan PH Pham HV Nguyen T Fox A Nguyen CV Do HQ Crusat M Farrar J Nguyen HT de Jong MD Horby P 《PloS one》2008,3(10):e3339
Background
Prior to 2007, highly pathogenic avian influenza (HPAI) H5N1 viruses isolated from poultry and humans in Vietnam were consistently reported to be clade 1 viruses, susceptible to oseltamivir but resistant to amantadine. Here we describe the re-emergence of human HPAI H5N1 virus infections in Vietnam in 2007 and the characteristics of the isolated viruses.Methods and Findings
Respiratory specimens from patients suspected to be infected with avian influenza in 2007 were screened by influenza and H5 subtype specific polymerase chain reaction. Isolated H5N1 strains were further characterized by genome sequencing and drug susceptibility testing. Eleven poultry outbreak isolates from 2007 were included in the sequence analysis. Eight patients, all of them from northern Vietnam, were diagnosed with H5N1 in 2007 and five of them died. Phylogenetic analysis of H5N1 viruses isolated from humans and poultry in 2007 showed that clade 2.3.4 H5N1 viruses replaced clade 1 viruses in northern Vietnam. Four human H5N1 strains had eight-fold reduced in-vitro susceptibility to oseltamivir as compared to clade 1 viruses. In two poultry isolates the I117V mutation was found in the neuraminidase gene, which is associated with reduced susceptibility to oseltamivir. No mutations in the M2 gene conferring amantadine resistance were found.Conclusion
In 2007, H5N1 clade 2.3.4 viruses replaced clade 1 viruses in northern Vietnam and were susceptible to amantadine but showed reduced susceptibility to oseltamivir. Combination antiviral therapy with oseltamivir and amantadine for human cases in Vietnam is recommended. 相似文献43.
Thi Nguyen Quynh Kozai Toyoki Heo Jeongwook Xuan Thai Du 《Plant Cell, Tissue and Organ Culture》2001,66(3):217-225
Effects of two ventilation methods (forced and natural) and two photosynthetic photon fluxes (PPF, 150 and 250 μmol m−2 s−1) on the photoautotrophic growth of in vitro cultured coffee (Coffea arabusta) plantlets were investigated. Number of air exchanges was 2.7, 5.9 and 3.9 h−1 for forced low rate, forced high rate and natural ventilation, respectively. Single node cuttings of in vitro cultured coffee plantlets were cultured on Florialite, a mixture of vermiculite and cellulose fibers with high air porosity,
emerged in liquid half strength basal MS medium, without sucrose, vitamins and plant growth regulators. The study included
40 days in the in vitro stage and 10 days in the ex vitro stage. Mean fresh and dry weights, leaf area, shoot and root lengths and net photosynthetic rate per plantlet were significantly
greater in forced high rate treatments compared with those in natural and forced low rate treatments. PPF had a distinct effect
on shoot length suppression and root elongation of coffee plantlets in forced high rate treatments. The control of carbon
dioxide concentration inside the culture box according to the plant demand when growing was easy with the forced ventilation
method in photoautotrophic micropropagation.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
44.
Diego A. Duarte Alexandros Papadimitriou Richard E. Gilbert Kerri Thai Yanling Zhang Mariana A. B. Rosales José B. Lopes de Faria Jacqueline M. Lopes de Faria 《PloS one》2016,11(2)
Bone marrow-derived cells were demonstrated to improve organ function, but the lack of cell retention within injured organs suggests that the protective effects are due to factors released by the cells. Herein, we tested cell therapy using early outgrowth cells (EOCs) or their conditioned media (CM) to protect the retina of diabetic animal models (type 1 and type 2) and assessed the mechanisms by in vitro study. Control and diabetic (db/db) mice (8 weeks of age) were randomized to receive a unique intravenous injection of 5×105EOCs or 0.25 ml thrice weekly tail-vein injections of 10x concentrated CM and Wystar Kyoto rats rendered diabetic were randomized to receive 0.50 ml thrice weekly tail-vein injections of 10x concentrated CM. Four weeks later, the animals were euthanized and the eyes were enucleated. Rat retinal Müller cells (rMCs) were exposed for 24 h to high glucose (HG), combined or not with EOC-conditioned medium (EOC-CM) from db/m EOC cultures. Diabetic animals showed increase in diabetic retinopathy (DR) and oxidative damage markers; the treatment with EOCs or CM infusions significantly reduced this damage and re-established the retinal function. In rMCs exposed to diabetic milieu conditions (HG), the presence of EOC-CM reduced reactive oxygen species production by modulating the NADPH-oxidase 4 system, thus upregulating SIRT1 activity and deacetylating Lys-310-p65-NFκB, decreasing GFAP and VEGF expressions. The antioxidant capacity of EOC-CM led to the prevention of carbonylation and nitrosylation posttranslational modifications on the SIRT1 molecule, preserving its activity. The pivotal role of SIRT1 on the mode of action of EOCs or their CM was also demonstrated on diabetic retina. These findings suggest that EOCs are effective as a form of systemic delivery for preventing the early molecular markers of DR and its conditioned medium is equally protective revealing a novel possibility for cell-free therapy for the treatment of DR. 相似文献
45.
46.
Guan-Sheng Jiao Seongjin Kim Mahtab Moayeri April Thai Lynne Cregar-Hernandez Linda McKasson Sean OMalley Stephen H. Leppla Alan T. Johnson 《Bioorganic & medicinal chemistry letters》2018,28(2):134-139
Anthrax is a highly lethal disease caused by the Gram-(+) bacteria Bacillus anthracis. Edema toxin (ET) is a major contributor to the pathogenesis of disease in humans exposed to B. anthracis. ET is a bipartite toxin composed of two proteins secreted by the vegetative bacteria, edema factor (EF) and protective antigen (PA). Our work towards identifying a small molecule inhibitor of anthrax edema factor is the subject of this letter. First we demonstrate that the small molecule probe 5′-Fluorosulfonylbenzoyl 5′-adenosine (FSBA) reacts irreversibly with EF and blocks enzymatic activity. We then show that the adenosine portion of FSBA can be replaced to provide more drug-like molecules which are up to 1000-fold more potent against EF relative to FSBA, display low cross reactivity when tested against a panel of kinases, and are nanomolar inhibitors of EF in a cell-based assay of cAMP production. 相似文献
47.
Ankit X. Sharma Ezekiel B. Quittner-Strom Young Lee Joshua A. Johnson Sarah A. Martin Xinxin Yu Jianping Li John Lu Zheqing Cai Shiuhwei Chen May-yun Wang Yiyi Zhang Mackenzie J. Pearson Andie C. Dorn Jeffrey G. McDonald Ruth Gordillo Hai Yan Dung Thai William L. Holland 《Cell reports》2018,22(7):1760-1773
48.
Phylogeny of the M superhaplogroup inferred from complete mitochondrial genome sequence of Indian specific lineages
下载免费PDF全文
![点击此处可从《Genome biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Revathi Rajkumar Jheelam Banerjee Hima Bindu Gunturi R Trivedi VK Kashyap 《Genome biology》2004,6(2):P3
Background
Phylogenetic analysis of human complete mitochondrial DNA sequences has largely contributed to resolving phylogenies and antiquity of different lineages belonging to the majorhaplogroups L, N and M (East-Asian lineages). In the absence of whole mtDNA sequence information of M lineages reported in India that exhibits highest diversity within the sub-continent, the present study was undertaken to provide a detailed analysis of this haplogroup to precisely characterize the lineages and unravel their intricate phylogeny. 相似文献49.
Karin G. Michels-Rautenstrauss Christian Y. Mardin Wido M. Budde Thomas Liehr J. Polansky Thai Nguyen Vincent Timmerman C. Van Broeckhoven Gottfried O. H. Naumann Rudolf A. Pfeiffer B. W. Rautenstrauss 《Human genetics》1998,102(1):103-106
Autosomal dominant juvenile open angle glaucoma (JOAG) is an early-onset form of primary open angle glaucoma (POAG), which
has been linked to chromosome 1q21–q31. Recently, mutations in the trabecular meshwork inducible glucocorticoid response gene
(TIGR), one of the candidate genes mapped in this region, were identified in glaucoma patients of several families. We screened
for mutations of the TIGR gene in two German families with JOAG and in 100 unselected sporadic cases of POAG. In the first
family we identified a Pro370Leu mutation and in the second family a Gly367Arg mutation cosegregating with the glaucoma phenotype.
No pathogenic mutation was found in 100 sporadic cases but a Tyr347Tyr polymorphism was found in two patients. Furthermore,
fluorescence in situ hybridization (FISH) analysis was used to map a TIGR-specific yeast artificial chromosome to 1q24.3–q25.2.
Received: 19 June 1997 / Accepted: 12 August 1997 相似文献
50.
Differential Genomic Effects of Six Different TiO2 Nanomaterials on Human Liver HepG2 Cells
下载免费PDF全文
![点击此处可从《Journal of biochemical and molecular toxicology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Sheau‐Fung Thai Kathleen A. Wallace Carlton P. Jones Hongzu Ren Eric Grulke Benjamin T. Castellon James Crooks Kirk T. Kitchin 《Journal of biochemical and molecular toxicology》2016,30(7):331-341
Human HepG2 cells were exposed to six TiO2 nanomaterials (with dry primary particle sizes ranging from 22 to 214 nm, either 0.3, 3, or 30 μg/mL) for 3 days. Some of these canonical pathways changed by nano‐TiO2 in vitro treatments have been already reported in the literature, such as NRF2‐mediated stress response, fatty acid metabolism, cell cycle and apoptosis, immune response, cholesterol biosynthesis, and glycolysis. But this genomic study also revealed some novel effects such as protein synthesis, protein ubiquitination, hepatic fibrosis, and cancer‐related signaling pathways. More importantly, this genomic analysis of nano‐TiO2 treated HepG2 cells linked some of the in vitro canonical pathways to in vivo adverse outcomes: NRF2‐mediated response pathways to oxidative stress, acute phase response to inflammation, cholesterol biosynthesis to steroid hormones alteration, fatty acid metabolism changes to lipid homeostasis alteration, G2/M cell checkpoint regulation to apoptosis, and hepatic fibrosis/stellate cell activation to liver fibrosis. 相似文献