全文获取类型
收费全文 | 446篇 |
免费 | 36篇 |
国内免费 | 10篇 |
出版年
2024年 | 2篇 |
2023年 | 2篇 |
2022年 | 12篇 |
2021年 | 10篇 |
2020年 | 10篇 |
2019年 | 14篇 |
2018年 | 23篇 |
2017年 | 14篇 |
2016年 | 19篇 |
2015年 | 19篇 |
2014年 | 106篇 |
2013年 | 16篇 |
2012年 | 18篇 |
2011年 | 23篇 |
2010年 | 25篇 |
2009年 | 19篇 |
2008年 | 21篇 |
2007年 | 17篇 |
2006年 | 16篇 |
2005年 | 9篇 |
2004年 | 9篇 |
2003年 | 8篇 |
2002年 | 8篇 |
2001年 | 7篇 |
2000年 | 3篇 |
1999年 | 8篇 |
1998年 | 6篇 |
1997年 | 2篇 |
1996年 | 8篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1991年 | 4篇 |
1990年 | 4篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1986年 | 3篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1974年 | 1篇 |
1973年 | 2篇 |
排序方式: 共有492条查询结果,搜索用时 15 毫秒
391.
Jin LZ Marquardt RR Baidoo SK Frohlich AA 《FEMS immunology and medical microbiology》2000,27(1):17-22
The objectives of this study were to investigate the nature of, and to purify K88ac fimbrial adhesin-specific receptors in the mucus from the small intestine of piglet. Adhesion was studied by incubating (3)H-labeled Escherichia coli with mucus that were treated with or without pronase, proteinase, trypsin or sodium metaperiodate. The results indicated that treatment with either proteolytic enzymes or sodium metaperiodate (to oxidize sugars) significantly reduced E. coli K88ac or K88+MB adhesion to the mucus, suggesting that the K88ac and K88+MB specific receptors in this preparation were, at least in part, glycoprotein in nature. The K88+MB fimbriae specific receptor was purified using affinity chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified K88+MB specific receptor together with the above data suggested that the receptor from the mucus of the small intestine of the pig was a 80-kDa glycoprotein. 相似文献
392.
Isotopic and genetic analyses of a mass grave in central California: Implications for precontact hunter‐gatherer warfare
下载免费PDF全文
![点击此处可从《American journal of physical anthropology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
393.
Development of chemoresistance is a major impediment to successful treatment of patients suffering from epithelial ovarian carcinoma (EOC). Among various molecular factors, presence of MyD88, a component of TLR-4/MyD88 mediated NF-κB signaling in EOC tumors is reported to cause intrinsic paclitaxel resistance and poor survival. However, 50–60% of EOC patients do not express MyD88 and one-third of these patients finally relapses and dies due to disease burden. The status and role of NF-κB signaling in this chemoresistant MyD88negative population has not been investigated so far. Using isogenic cellular matrices of cisplatin, paclitaxel and platinum-taxol resistant MyD88negative A2780 ovarian cancer cells expressing a NF-κB reporter sensor, we showed that enhanced NF-κB activity was required for cisplatin but not for paclitaxel resistance. Immunofluorescence and gel mobility shift assay demonstrated enhanced nuclear localization of NF-κB and subsequent binding to NF-κB response element in cisplatin resistant cells. The enhanced NF-κB activity was measurable from in vivo tumor xenografts by dual bioluminescence imaging. In contrast, paclitaxel and the platinum-taxol resistant cells showed down regulation in NF-κB activity. Intriguingly, silencing of MyD88 in cisplatin resistant and MyD88positive TOV21G and SKOV3 cells showed enhanced NF-κB activity after cisplatin but not after paclitaxel or platinum-taxol treatments. Our data thus suggest that NF-κB signaling is important for maintenance of cisplatin resistance but not for taxol or platinum-taxol resistance in absence of an active TLR-4/MyD88 receptor mediated cell survival pathway in epithelial ovarian carcinoma. 相似文献
394.
Eu3+‐activated MAl(SO4)2Br phosphors (where M = Mg or Sr) are successfully prepared using a wet chemical reaction technique. The samples are characterized by X‐ray diffraction (XRD) and photoluminescence (PL) spectroscopies. The XRD pattern revealed that both the samples are microcrystalline in nature. PL of Eu3+‐doped SrAl(SO4)2Br and MgAl(SO4)2Br phosphors exhibited characteristic red emission coming from the 5D0 → 7F2 (616 nm) electron transition, when excited by 396 nm wavelength of light. The maximum intensity of luminescence was observed at a concentration of 1 mol% Eu3+. The intensity of the electric dipole transition at 616 nm is greater than that of the magnetic dipole transition at 594 nm. The results showed that MAl(SO4)2Br:Eu3+, (M = Mg, Sr) phosphors have potential application in near‐UV light‐emitting diodes as efficient red‐emitting phosphor. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
395.
Guangda Xin Shaoyou Qin Song Wang Xu Wang Yonggui Zhang Jiangbin Wang 《Experimental biology and medicine (Maywood, N.J.)》2015,240(10):1279-1286
Recent research has shown that the occurrence of gender disparity in liver cancer associated with sex differences in MyD88-dependent IL-6 production, but the role of this signaling pathway in sex differences of non-alcoholic steatohepatitis (NASH) remains unknown. To investigate the effects of sex hormone-specific intervention on pathology and progression of NASH, and on the inflammatory TLR-MyD88-IL-6 signaling pathway NASH was modeled in C57/BL6 mice by feeding a methionine and choline-deficient (MCD) diet for 4 weeks. Male mice were subjected to sex hormone-related interventions such as orchidectomy, and orchidectomy combined with administration of either testosterone propionate or estradiol benzoate. Next, the degree of non-alcoholic fatty liver disease activity score (NAS), serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and the expression level of MyD88 and IL-6, were compared between these groups. Males developed more serious inflammatory problems and had a higher NAS than the females. Sex-specific intervention in male mice by orchidectomy reduced NAS, ALT, and AST, and the expression level of MyD88 and IL-6. But administration of exogenous androgen had no influence on either NAS or the expression of ALT, AST, MyD88, and IL-6. On the other hand, exogenous estrogen could alleviate the pathological damage caused by NASH, as well as reduce NAS, ALT and AST, and the expression of MyD88 and IL-6. The result show different sex hormone-related interventions affected the severity of NASH, possibly by modulating the level of sex hormones and regulating the TLR-MyD88-IL-6 signaling pathway. 相似文献
396.
Jinlai Lei Yahui Fu Yan Zhuang Kun Zhang Daigang Lu 《Journal of cellular physiology》2019,234(12):23160-23168
miR-382-3p has been reported to be upregulated in synovial membrane in knee osteoarthritis (OA). Nevertheless, its role in OA remains largely unknown. The aim of this study was to investigate the specific function and mechanisms of miR-382-3p in the course of OA. In this study, human OA chondrocytes were pretreated with interleukin-1β (IL-1β) at 5 ng/ml for 12 hr to stimulate inflammatory response and matrix metalloproteinases (MMPs) expression in chondrocytes. Meanwhile, miR-382-3p was downregulated in IL-1β-stimulated chondrocytes. In addition, we found that miR-382-3p directly interacts with connexin 43 (CX43) and attenuates the increase of cytochrome c oxidase polypeptide II, inducible nitric oxide synthase, and MMP-1/13 that is induced by IL-1β. Furthermore, our observations indicated that miR-382-3p inhibited the expression of Toll-like receptor 4 (TLR4), Myeloid differentiation primary response 88 (MyD88) and nuclear factor κB (NF-κB) in IL-1β-stimulated chondrocytes, while CX43 overexpression could partly reverse these decreases. In conclusion, miR-382-3p participated in OA may through the TLR4/MyD88/NF-κB signaling pathway by directly targeting CX43. 相似文献
397.
398.
Fulminant hepatic failure (FHF) is a lethal clinical syndrome characterized by the activation of macrophages and the increased production of inflammatory mediators. The purpose of this study was to investigate the effects of neohesperidin dihydrochalcone (NHDC), a widely-used low caloric artificial sweetener against FHF. An FHF experimental model was established in mice by intraperitoneal injection of D-galactosamine (d-GalN) (400 mg/kg)/lipopolysaccharides (LPS) (10 μg/kg). Mice were orally administered NHDC for 6 continuous days and at 1 h before d-GalN/LPS administration. RAW264.7 macrophages were used as an in vitro model. Cells were pre-treated with NHDC for 1 h before stimulation with LPS (10 μg/ml) for 6 h. d-GalN/LPS markedly increased the serum transaminase activities and levels of oxidative and inflammatory markers, which were significantly attenuated by NHDC. Mechanistic analysis indicated that NHDC inhibited LPS-induced myeloid differentiation factor 88 (MyD88) and TIR-containing adapter molecule (TRIF)-dependent signaling. Transient transfection of TLR4 or MyD88 siRNA inhibited the downstream inflammatory signaling. This effect could also be achieved by the pretreatment with NHDC. The fluorescence microscopy and flow cytometry results suggested that NHDC potently inhibited the binding of LPS to TLR4 in RAW264.7 macrophages. In addition, the inhibitory effect of NHDC on LPS-induced translocation of TLR4 into lipid raft domains played an important role in the amelioration of production of downstream pro-inflammatory molecules. Furthermore, the activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) by NHDC inhibited TLR4 signaling. In conclusion, our results suggest that NHDC attenuates d-GalN/LPS-induced FHF by inhibiting the TLR4-mediated inflammatory pathway, demonstrating a new application of NHDC as a hepatoprotective agent. 相似文献
399.
Y.-J. Lin L. Loys † J.-C. Shiao ‡ Y. Iizuka § W.-N. Tzeng 《Journal of fish biology》2007,71(6):1773-1787
European eels Anguilla anguilla from freshwater lakes in Lithuania had slower growth rates and lower backcalculated total lengths ( L T ) than those from lagoons and coastal waters, but no significant differences were found among fish with different migratory histories or between naturally recruited and stocked fish except a higher L T at age of stocked European eels at ages 5 to 8 years. The asymptotic L T did not differ among habitats or migratory histories, but the stocked eels in the lakes had smaller K (coefficient from the von Bertalanffy growth function) than did the both naturally recruited and stocked eels in the lagoon and coastal waters. The growth rate of European eels in Lithuania might be influenced mainly by different habitats rather than different migratory histories and stocking. The lower L T at age of naturally recruited fish at ages 5–8 years compared to stocked fish might result from the extra energy costs entailed in migration from the Atlantic and across the Baltic Sea. 相似文献
400.
Migration flexibility between freshwater and marine habitats of the pond smelt Hypomesus nipponensis
The life histories of the pond smelt Hypomesus nipponensis collected from Japanese fresh waters and brackish (sea) waters were studied by examining the strontium (Sr) and calcium (Ca) concentrations in their otoliths. The Sr:Ca ratios in the otoliths changed with the salinity of the habitat. The pond smelt living in a freshwater environment showed consistently low Sr:Ca ratios throughout the otolith, averaging 1·2–1·3 × 10−3 . These samples were identified as a standard freshwater type. In contrast, fish collected from the intertidal zone showed higher otolith Sr:Ca ratios than those in the standard freshwater type, and the ratios fluctuated along the growth phase. In addition to the two representative life‐history types of H. nipponensis , i. e . freshwater and anadromous life‐history types, other pond smelts were found to have an estuarine resident life history‐type with no freshwater phase, indicating that the pond smelt has a flexible migration strategy with a high degree of behavioural plasticity and an ability to utilize the full range of salinity in its life history. 相似文献