全文获取类型
收费全文 | 645篇 |
免费 | 55篇 |
出版年
2023年 | 3篇 |
2021年 | 11篇 |
2020年 | 8篇 |
2019年 | 14篇 |
2018年 | 15篇 |
2017年 | 13篇 |
2016年 | 13篇 |
2015年 | 28篇 |
2014年 | 40篇 |
2013年 | 47篇 |
2012年 | 49篇 |
2011年 | 50篇 |
2010年 | 36篇 |
2009年 | 20篇 |
2008年 | 31篇 |
2007年 | 27篇 |
2006年 | 28篇 |
2005年 | 22篇 |
2004年 | 22篇 |
2003年 | 26篇 |
2002年 | 23篇 |
2001年 | 16篇 |
2000年 | 14篇 |
1999年 | 15篇 |
1998年 | 3篇 |
1997年 | 12篇 |
1996年 | 4篇 |
1995年 | 6篇 |
1994年 | 6篇 |
1993年 | 2篇 |
1992年 | 11篇 |
1991年 | 4篇 |
1989年 | 9篇 |
1987年 | 3篇 |
1984年 | 4篇 |
1983年 | 4篇 |
1982年 | 3篇 |
1981年 | 6篇 |
1979年 | 5篇 |
1978年 | 7篇 |
1977年 | 3篇 |
1976年 | 6篇 |
1975年 | 6篇 |
1974年 | 6篇 |
1973年 | 4篇 |
1972年 | 3篇 |
1971年 | 4篇 |
1968年 | 1篇 |
1965年 | 1篇 |
1960年 | 1篇 |
排序方式: 共有700条查询结果,搜索用时 15 毫秒
71.
Jianmin Meng Egil Lien Douglas T. Golenbock 《The Journal of biological chemistry》2010,285(12):8695-8702
Lipopolysaccharide (LPS) activates innate immune responses through TLR4·MD-2. LPS binds to the MD-2 hydrophobic pocket and bridges the dimerization of two TLR4·MD-2 complexes to activate intracellular signaling. However, exactly how lipid A, the endotoxic moiety of LPS, activates myeloid lineage cells remains unknown. Lipid IVA, a tetra-acylated lipid A precursor, has been used widely as a model for lipid A activation. For unknown reasons, lipid IVA activates proinflammatory responses in rodent cells but inhibits the activity of LPS in human cells. Using stable TLR4-expressing cell lines and purified monomeric MD-2, as well as MD-2-deficient bone marrow-derived macrophages, we found that both mouse TLR4 and mouse MD-2 are required for lipid IVA activation. Computational studies suggested that unique ionic interactions exist between lipid IVA and TLR4 at the dimerization interface in the mouse complex only. The negatively charged 4′-phosphate on lipid IVA interacts with two positively charged residues on the opposing mouse, but not human, TLR4 (Lys367 and Arg434) at the dimerization interface. When replaced with their negatively charged human counterparts Glu369 and Gln436, mouse TLR4 was no longer responsive to lipid IVA. In contrast, human TLR4 gained lipid IVA responsiveness when ionic interactions were enabled by charge reversal at the dimerization interface, defining the basis of lipid IVA species specificity. Thus, using lipid IVA as a selective lipid A agonist, we successfully decoupled and coupled two sequential events required for intracellular signaling: receptor engagement and dimerization, underscoring the functional role of ionic interactions in receptor activation. 相似文献
72.
Antihyperglycemic effect of polysaccharide from fermented broth of Pleurotus citrinopileatus 总被引:2,自引:0,他引:2
Pleurotus citrinopileatus is an edible mushroom, which has recently become very popular, with a consequent increase in industrial production. Water-soluble
polysaccharides (WSPS), extracted from edible mushrooms, have been found to have antitumor and immunoenhancing effects. In
this study, we investigate the effects of WSPS extracted from submerged fermented medium of P. citrinopileatus on hyperglycemia and damaged pancreatic cells in rats with streptozotocin (STZ)-induced diabetes. The diabetic rats fed with
water-soluble polysaccharide of P. citrinopileatus (SPPC) lost less body weight than those fed SPPC-free regular diet. Serum total cholesterol and triglyceride levels in the
diabetic rats fed with SPPC at a dose of 0.4 g/kg bw daily was lower than in the groups fed with SPPC at doses of 0.04 and
0.12 g/kg bw. The fasting blood glucose levels of diabetic rats fed with SPPC were 44% lower than the negative controls. The
degree of damage to the islets of Langerhans of the rats fed with the highest dosage of SPPC was significantly lower than
those fed with SPPC at doses of 0.04 and 0.12 g/kg bw. The results showed that STZ-induced diabetic rats fed with SPPC might
help alleviate the elevation of the level of that in fasting blood glucose. 相似文献
73.
74.
Fong YC Lin CY Su YC Chen WC Tsai FJ Tsai CH Huang CY Tang CH 《Journal of cellular physiology》2012,227(1):223-232
Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. CCN6 is a cysteine-rich protein that belongs to the CCN (Cyr61, CTGF, and Nov) family of matricellular proteins. However, the effects of CCN6 on human chondrosarcoma cells are largely unknown. In this study, we found that CCN6 increased the migration and the expression of intercellular adhesion molecule-1 (ICAM-1) in human chondrosarcoma cells. αvβ3 and αvβ5 integrin monoclonal antibody and mitogen-activated protein kinase (MEK) inhibitors (PD98059 and U0126) inhibited the CCN6-induced increase of the migration and ICAM-1 up-regulation of chondrosarcoma cells. CCN6 stimulation increased the phosphorylation of focal adhesion kinase (FAK), MEK, and extracellular signal-regulated kinase (ERK). In addition, activator protein-1 (AP-1) inhibitors suppressed the cell migration and ICAM-1 expression enhanced by CCN6. Moreover, CCN6 increased AP-1 luciferase activity and binding of c-Jun to the AP-1 element on the ICAM-1 promoter. Taken together, our results indicate that CCN6 enhances the migration of chondrosarcoma cells by increasing ICAM-1 expression through the αvβ3 and αvβ5 integrin receptor, FAK, MEK, ERK, c-Jun, and AP-1 signal transduction pathway. 相似文献
75.
Lien CF Molnár E Toman P Tsibouklis J Pilkington GJ Górecki DC Barbu E 《Biomacromolecules》2012,13(4):1067-1073
A series of O-substituted alkylglyceryl chitosans with systematically varied alkyl chain length and degree of grafting has been employed for the formulation of aqueous nanoparticulate systems, which were in turn investigated for their effects on a modeled blood-brain-barrier system of mouse-brain endothelial cells. Barrier function measurements employing electric cell-substrate impedance sensing and analyses of tight junction-specific protein profiles have indicated that the alkylglyceryl-modified chitosan nanoparticles impact upon the integrity of the model blood-brain barrier, whereas confocal microscopy experiments have demonstrated the efficient cellular uptake and the perinuclear localization of these nanoparticles. The application of nanoparticles to the model blood-brain barrier effected an increase in its permeability, as demonstrated by following the transport of the tracer molecule fluorescein isothiocyanate. 相似文献
76.
Ho Dang Trung N Le Thi Phuong T Wolbers M Nguyen Van Minh H Nguyen Thanh V Van MP Thieu NT Van TL Song DT Thi PL Thi Phuong TN Van CB Tang V Ngoc Anh TH Nguyen D Trung TP Thi Nam LN Kiem HT Thi Thanh TN Campbell J Caws M Day J de Jong MD Van Vinh CN Van Doorn HR Tinh HT Farrar J Schultsz C;VIZIONS CNS Infection Network 《PloS one》2012,7(5):e37825
77.
78.
79.
We describe here a protocol for culturing epicardial cells from adult zebrafish hearts, which have a unique regenerative capacity after injury. Briefly, zebrafish hearts first undergo ventricular amputation or sham operation. Next, the hearts are excised and explanted onto fibrin gels prepared in advance in a multiwell tissue culture plate. The procedure allows the epicardial cells to outgrow from the ventricle onto a fibrin matrix in vitro. This protocol differs from those used in other organisms by using a fibrin gel to mimic blood clots that normally form after injury and that are essential for proper cell migration. The culture procedure can be accomplished within 5 h; epicardial cells can be obtained within 24-48 h and can be maintained in culture for 5-6 d. This protocol can be used to investigate the mechanisms underlying epicardial cell migration, proliferation and epithelial-to-mesenchymal transition during heart regeneration, homeostatic cardiac growth or other physiological processes. 相似文献
80.
Recruitment and endo-lysosomal activation of TLR9 in dendritic cells infected with Trypanosoma cruzi