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741.
Jieun Choo Gwangbeom Heo Su Jin Kim Yunna Lee Akihito Ishigami Naoki Maruyama Hae Young Chung Eunok Im 《生物化学与生物物理学报:疾病的分子基础》2018,1864(12):3668-3678
Senescence marker protein 30 (SMP30) is a calcium-binding protein whose expression decreases during senescence. SMP30 deficiency increases susceptibility to cytokine-induced apoptosis in the liver and to radiation-induced apoptosis in the small intestine. Furthermore, colonic epithelial cell death is associated with the severity of colitis. Therefore, in the present study, we investigated the function of SMP30 during intestinal inflammation. In SMP30 deficient mice, colitis was significantly exacerbated as demonstrated by increased mortality (p?=?0.001), body weight loss (p?=?0.0105 at day 8), rectal bleeding (p?=?0.0047 at day 8) and diarrhea (p?=?0.0030 at day 8), histological scores (ulcers, p?=?0.0002; edema, p?=?0.0125; leukocyte infiltration, p?=?0.0016) and productions of pro-inflammatory cytokines (IL-1α, p?=?0.0452; IL-6, p?=?0.0074; G-CSF, p?=?0.0036). In addition, greater proportions of apoptotic cells and lower levels of anti-apoptotic marker proteins (total PARP-1 and Bcl-2) were observed in the inflamed intestines of SMP30 deficient mice than in wild type controls. In vitro experiments on colonic epithelial cells showed that stable SMP30 expression inhibited but that SMP30 siRNA expression increased TNF-α-induced apoptosis. SMP30 inhibition decreased Nrf2 mRNA expression levels (p?<?0.0001), but SMP30 overexpression increased Nrf2 mRNA expression levels (p?=?0.0495). The underlying mechanism by which SMP30 protected cells appeared to be by inhibiting Nrf2 ubiquitination and Keap1 expression, and thus enhancing Nrf2 activity. Moreover, SMP30 deficiency increased the incidence of colitis-associated colon cancer as determined by increased mortality (p?=?0.0572) and average polyp number (p?=?0.0277). Collectively, these findings suggest that SMP30 protects intestinal epithelial cells from apoptosis and this can contribute to amelioration of colitis and colitis-associated colon cancer. 相似文献
742.
Batten disease (BD)—also known as juvenile neuronal ceroid lipofuscinoses—is an inherited neurodegenerative disorder caused by CLN3 gene mutations. Although CLN3-related oxidative and mitochondrial stresses have been studied in BD, the pathologic mechanism of the disease is not clearly understood. To address the molecular factors linked to high levels of oxidative stress in BD, we examined the expression of mitochondria-related metabolic molecules, including pyruvate dehydrogenase (PDH), ATP citrate lyase (ACL), and phosphoenolpyruvate carboxykinase (PEPCK), as well as the apoptosis-related ganglioside, acetyl-GD3. We observed an increased expression of PDH and a decreased expression of ACL, PEPCK, and acetyl-GD3 in BD lymphoblast cells compared to normal cells, possibly resulting in the high ROS levels, mitochondrial membrane depolarization, and apoptosis typically found in BD. 相似文献
743.
Sung-Mok Lee Baek-Rock Oh Jang Min Park Anna Yu Sun-Yeon Heo Won-Kyung Hong Jeong-Woo Seo Chul Ho Kim 《Biotechnology and Bioprocess Engineering》2013,18(6):1210-1215
To obtain high-yield production of 2,3-butanediol (2,3-BD) from glucose, we optimized the culture conditions for a lactate dehydrogenase-deficient mutant (ΔldhA) of Klebsiella pneumoniae using response surface methodology. 2,3-BD production was successfully improved by optimizing pH (5.6), aeration (3.50 vvm) and concentration of corn steep liquor (45.0 mL/L) as a nitrogen source, resulting in a maximum level of 2,3-BD production of 148.8 g/L and productivity of 2.48 g/L/h. 2,3-BD was also obtained with high concentration (76.24 g/L) and productivity (2.31 g/L/h) from the K. pneumoniae mutant strain using sugarcane molasses as a carbon source. 相似文献
744.
Yoony YJ Gent Karin Weijers Carla FM Molthoff Albert D Windhorst Marc C Huisman Desirée EC Smith Sumith A Kularatne Gerrit Jansen Philip S Low Adriaan A Lammertsma Conny J van der Laken 《Arthritis research & therapy》2013,15(2):R37
Introduction
Detection of (subclinical) synovitis is relevant for both early diagnosis and monitoring of therapy of rheumatoid arthritis (RA). Previously, the potential of imaging (sub)clinical arthritis was demonstrated by targeting the translocator protein in activated macrophages using (R)-[11C]PK11195 and positron emission tomography (PET). Images, however, also showed significant peri-articular background activity. The folate receptor (FR)-β is a potential alternative target for imaging activated macrophages. Therefore, the PET tracer [18F]fluoro-PEG-folate was synthesized and evaluated in both in vitro and ex vivo studies using a methylated BSA induced arthritis model.Methods
[18F]fluoro-PEG-folate was synthesized in a two-step procedure. Relative binding affinities of non-radioactive fluoro-PEG-folate, folic acid and naturally circulating 5-methyltetrahydrofolate (5-Me-THF) to FR were determined using KB cells with high expression of FR. Both in vivo [18F]fluoro-PEG-folate PET and ex vivo tissue distribution studies were performed in arthritic and normal rats and results were compared with those of the established macrophage tracer (R)-[11C]PK11195.Results
[18F]fluoro-PEG-folate was synthesized with a purity >97%, a yield of 300 to 1,700 MBq and a specific activity between 40 and 70 GBq/µmol. Relative in vitro binding affinity for FR of F-PEG-folate was 1.8-fold lower than that of folic acid, but 3-fold higher than that of 5-Me-THF. In the rat model, [18F]fluoro-PEG-folate uptake in arthritic knees was increased compared with both contralateral knees and knees of normal rats. Uptake in arthritic knees could be blocked by an excess of glucosamine-folate, consistent with [18F]fluoro-PEG-folate being specifically bound to FR. Arthritic knee-to-bone and arthritic knee-to-blood ratios of [18F]fluoro-PEG-folate were increased compared with those of (R)-[11C]PK11195. Reduction of 5-Me-THF levels in rat plasma to those mimicking human levels increased absolute [18F]fluoro-PEG-folate uptake in arthritic joints, but without improving target-to-background ratios.Conclusions
The novel PET tracer [18F]fluoro-PEG-folate, designed to target FR on activated macrophages provided improved contrast in a rat model of arthritis compared with the accepted macrophage tracer (R)-[11C]PK11195. These results warrant further exploration of [18F]fluoro-PEG-folate as a putative PET tracer for imaging (sub)clinical arthritis in RA patients. 相似文献745.
Eun-Kyung Kim Yong-Oon Ahn Saerom Kim Tae Min Kim Bhumsuk Keam Dae Seog Heo 《Cytotherapy》2013,15(2):231-241.e1
Background aimsCulturing natural killer (NK) cells from patients with advanced cancer is difficult and has restricted the generation of sufficient cell numbers for autologous adoptive NK-cell therapy. The aim of this study was to establish a novel method for ex vivo NK-cell expansion from patients with cancer.MethodsNK cells (CD3?CD56+) were isolated from peripheral blood mononuclear cells from healthy volunteers and cancer patients, and NK? fractions were used as feeder cells. Purified NK cells were co-cultured with feeder cells in AIM-V medium (Invitrogen, Carlsbad, CA, USA) supplemented with 5% human serum and 1000 units/mL human interleukin-2.ResultsNK cells co-cultured with feeder cells from healthy volunteers (feeder-HV) expanded more than NK cells co-cultured with feeder cells from cancer patients (feeder-CP). During the 14-day culture period, NK cells from patients with advanced cancer co-cultivated with feeder-HV expanded on average 300-fold. NK cells co-cultivated with feeder-CP expanded on average 169.4-fold. Cultures grown in the presence of feeder-HV contained 93.8 ± 7.0% (mean ± standard deviation; n = 6) CD3?CD56+ NK cells, and cultures grown in the presence of feeder-CP contained 83.6 ± 15.9% CD3?CD56+ NK cells. Feeder-HV caused a relative increase in CD3+CD4+ T cells, whereas feeder-CP did not induce changes. Interleukin-15, a cytokine that induces NK-cell proliferation, was detected in the culture supernatants of feeder-HV but not in those of feeder-CP.ConclusionsFeeder cells obtained from healthy volunteers have the potential to expand and activate NK cells from patients with advanced cancer. The novel NK-cell expansion method described here provides a technique for acquiring the large numbers of highly active NK cells from patients with cancer for autologous adoptive immunotherapy. 相似文献
746.
Wan Heo Eui Seop Lee Hyung Taek Cho Jun Ho Kim Jin Hyup Lee Seok Min Yoon 《Bioscience, biotechnology, and biochemistry》2013,77(11):1964-1972
ABSTRACTThis study was designed to select potent cholesterol-lowering probiotic strains on HepG2 cell and investigate the effect of selected strain, Lactobacillus plantarum LRCC 5273 and LRCC 5279 in hypercholesterolemic mice. In the results, LP5273 group showed significantly reduced total and LDL cholesterol compared to HCD group. In addition to significantly up-regulated hepatic mRNA expression of LXR-α and CYP7A1, intestinal LXR-α and ABCG5 were significantly up-regulated in LP5273 group. With activation of hepatic and intestinal LXR-α and its target genes, fecal cholesterol and bile acid excretion were increased in LP5273 fed mice. These results suggest that LP5273 ameliorates hypercholesterolemia in mice through the activation of hepatic and intestinal LXR-α, resulting in enhancement of fecal cholesterol and bile acids excretion in the small intestine. The results of present study suggest mechanistic evidences for hypocholesterolemic effects of L. plantarum spp., and may contribute to future researches for prevention of hypercholesterolemia and cardiovascular disease. 相似文献
747.
Jo Dong Hyun Kim Jin Hyoung Heo Jong-Ik Kim Jeong Hun Cho Chung-Hyun 《Molecules and cells》2013,36(5):465-471
The hyaloid vessel is a transient vascular network that nourishes the lens and the primary vitreous in the early developmental periods. In hyaloid vessels devoid of the support of astrocytes, we demonstrate that tight junction proteins, zonula occludens-1 and occludin, are regularly expressed at the junction of endothelial cells. To figure out the factor influencing the formation of tight junctions in hyaloid vessels, we further progress to investigate the interactions between endothelial cells and pericytes, two representative constituent cells in hyaloid vessels. Interestingly, endothelial cells interact with pericytes in the early postnatal periods and the interaction between two cell types provokes the up-regulation of transforming growth factor β1. Further in vitro experiments demonstrate that transforming growth factor β1 induces the activation of Smad2 and Smad3 and the formation of tight junction proteins. Taken together, in hyaloid vessels, pericytes seem to regulate the formation of tight junctions by the interaction with endothelial cells even without the support of astrocytes. Additionally, we suggest that the hyaloid vessel is a valuable system that can be utilized for the investigation of cell-cell interaction in the formation of tight junctions in developing vasculatures. 相似文献
748.
Ji Young Ko Young Dae Kim Yoo Jin Hong Hye-Jeong Lee Jin Hur Byoung Wook Choi Ji Hoe Heo Young Jin Kim 《PloS one》2013,8(10)
Background and Purpose
Clinical significance of out-pouching structures of the left atrium (LA) as potential embolic sources remains unclear. We sought to evaluate the association between stroke and LA out-pouching structures.Methods
A case-control study was conducted to assess the prevalence of LA out-pouching structures in subjects with and without stroke. Case subjects were 270 stroke patients who had undergone cardiac CT. Control subjects were 270 age- and sex-matched patients without a history of stroke and who had undergone cardiac CT. Presence of LA out-pouching structures was determined by ECG-gated cardiac CT. The location of out-pouching structures was categorized as near Bachmann bundle, anterior, inferoseptal, inferior, and lateral. The prevalence, number and location of out-pouching structures and clinical characteristics were compared between the two groups.Results
One hundred sixty eight out-pouching structures were identified in 139 stroke patients (51%), while a total of 169 out-pouching structures were found in 155 control patients (57%) (p=0.1949). The prevalence of LA out-pouching structures with different locations was not significantly different between the stroke group and control group. In the stroke group, the prevalence of out-pouching structures was not significantly different by subtypes of ischemic stroke and the prevalence of LA out-pouching structures was not different between patients with atrial fibrillation (AF) and without AF.Conclusion
The left atrial out-pouching structures are commonly seen in a population with and without stroke with similar prevalence. Our study suggests that LA out-pouching structures are not significant risk factors of stroke. 相似文献749.
A network of Rab GTPases controls phagosome maturation and is modulated by Salmonella enterica serovar Typhimurium
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Smith AC Heo WD Braun V Jiang X Macrae C Casanova JE Scidmore MA Grinstein S Meyer T Brumell JH 《The Journal of cell biology》2007,176(3):263-268
Members of the Rab guanosine triphosphatase (GTPase) family are key regulators of membrane traffic. Here we examined the association of 48 Rabs with model phagosomes containing a non-invasive mutant of Salmonella enterica serovar Typhimurium (S. Typhimurium). This mutant traffics to lysosomes and allowed us to determine which Rabs localize to a maturing phagosome. In total, 18 Rabs associated with maturing phagosomes, each with its own kinetics of association. Dominant-negative mutants of Rab23 and 35 inhibited phagosome-lysosome fusion. A large number of Rab GTPases localized to wild-type Salmonella-containing vacuoles (SCVs), which do not fuse with lysosomes. However, some Rabs (8B, 13, 23, 32, and 35) were excluded from wild-type SCVs whereas others (5A, 5B, 5C, 7A, 11A, and 11B) were enriched on this compartment. Our studies demonstrate that a complex network of Rab GTPases controls endocytic progression to lysosomes and that this is modulated by S. Typhimurium to allow its intracellular growth. 相似文献
750.
Heo SK Yoon MA Lee SC Ju SA Choi JH Suh PG Kwon BS Kim BS 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(9):6305-6310
Herpes virus entry mediator (HVEM) is a member of the TNF receptor (TNFR) superfamily and is expressed on many immune cells, including T and B cells, NK cells, monocytes, and neutrophils. Interaction of HVEM with its ligand, LIGHT, costimulates T cells and increases the bactericidal activity of monocytes and neutrophils. The interaction recruits cytoplasmic TNFR-associated factor adaptor proteins to the intracellular domain of HVEM. This leads to NFkappaB activation as a result of IkappaBalpha degradation and/or JNK/AP-1 activation, and ultimately results in the expression of genes required for cell survival, cytokine production, or cell proliferation. In this study, we show that treatment of human monocytes with recombinant human LIGHT (rhLIGHT) induces rapid elevation of intracellular calcium concentration ([Ca(2+)](i)) in a HVEM-specific manner in parallel with TNF-alpha production, and enhances the bactericidal activities of monocytes. Immunoprecipitation and Western blotting analyses revealed phosphorylation of phospholipase Cgamma1 (PLCgamma1) but not PLCgamma2. rhLIGHT-induced Ca(2+)response was completely abolished by silencing PLCgamma1, or preincubating monocytes with PLC inhibitors, antagonists of the inositol-1,4,5-triphosphate receptor, or [Ca(2+)](i) chelators. Furthermore, these PLC/Ca(2+) inhibitors also blocked rhLIGHT-mediated IkappaBalpha degradation, generation of reactive oxygen species, TNF-alpha production and the bactericidal activities of monocytes. Our results indicate that Ca(2+)is a downstream mediator of the LIGHT/HVEM interaction in monocytes. 相似文献