全文获取类型
收费全文 | 1589篇 |
免费 | 152篇 |
出版年
2024年 | 1篇 |
2023年 | 12篇 |
2022年 | 7篇 |
2021年 | 81篇 |
2020年 | 51篇 |
2019年 | 66篇 |
2018年 | 71篇 |
2017年 | 53篇 |
2016年 | 76篇 |
2015年 | 118篇 |
2014年 | 120篇 |
2013年 | 126篇 |
2012年 | 144篇 |
2011年 | 139篇 |
2010年 | 77篇 |
2009年 | 58篇 |
2008年 | 97篇 |
2007年 | 81篇 |
2006年 | 55篇 |
2005年 | 59篇 |
2004年 | 54篇 |
2003年 | 41篇 |
2002年 | 41篇 |
2001年 | 7篇 |
2000年 | 7篇 |
1999年 | 5篇 |
1998年 | 12篇 |
1997年 | 8篇 |
1996年 | 5篇 |
1995年 | 8篇 |
1994年 | 5篇 |
1993年 | 7篇 |
1992年 | 8篇 |
1991年 | 6篇 |
1990年 | 6篇 |
1989年 | 2篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1979年 | 2篇 |
1977年 | 2篇 |
1974年 | 4篇 |
1973年 | 3篇 |
1971年 | 1篇 |
1968年 | 1篇 |
1966年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有1741条查询结果,搜索用时 15 毫秒
71.
PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties 总被引:1,自引:0,他引:1
Bouhlel MA Derudas B Rigamonti E Dièvart R Brozek J Haulon S Zawadzki C Jude B Torpier G Marx N Staels B Chinetti-Gbaguidi G 《Cell metabolism》2007,6(2):137-143
Th1 cytokines promote monocyte differentiation into proatherogenic M1 macrophages, while Th2 cytokines lead to an "alternative" anti-inflammatory M2 macrophage phenotype. Here we show that in human atherosclerotic lesions, the expression of M2 markers and PPARgamma, a nuclear receptor controlling macrophage inflammation, correlate positively. Moreover, PPARgamma activation primes primary human monocytes into M2 differentiation, resulting in a more pronounced anti-inflammatory activity in M1 macrophages. However, PPARgamma activation does not influence M2 marker expression in resting or M1 macrophages, nor does PPARgamma agonist treatment influence the expression of M2 markers in atherosclerotic lesions, indicating that only native monocytes can be primed by PPARgamma activation to an enhanced M2 phenotype. Furthermore, PPARgamma activation significantly increases expression of the M2 marker MR in circulating peripheral blood mononuclear cells. These data demonstrate that PPARgamma activation skews human monocytes toward an anti-inflammatory M2 phenotype. 相似文献
72.
73.
Giacomo Pozzoli Hany E. Marei Asma Althani Alma Boninsegna Patrizia Casalbore Lionel N. J. L. Marlier Giulia Lanzilli Manuela Zonfrillo Giovanna Petrucci Bianca Rocca Pierluigi Navarra Alessandro Sgambato Carlo Cenciarelli 《Journal of cellular physiology》2019,234(9):15459-15471
Several clinical studies indicated that the daily use of aspirin or acetylsalicylic acid reduces the cancer risk via cyclooxygenases (Cox-1 and Cox-2) inhibition. In addition, aspirin-induced Cox-dependent and -independent antitumor effects have also been described. Here we report, for the first time, that aspirin treatment of human glioblastoma cancer (GBM) stem cells, a small population responsible for tumor progression and recurrence, is associated with reduced cell proliferation and motility. Aspirin did not interfere with cell viability but induced cell-cycle arrest. Exogenous prostaglandin E2 significantly increased cell proliferation but did not abrogate the aspirin-mediated growth inhibition, suggesting a Cox-independent mechanism. These effects appear to be mediated by the increase of p21 waf1 and p27 Kip1, associated with a reduction of Cyclin D1 and Rb1 protein phosphorylation, and involve the downregulation of key molecules responsible for tumor development, that is, Notch1, Sox2, Stat3, and Survivin. Our results support a possible role of aspirin as adjunctive therapy in the clinical management of GBM patients. 相似文献
74.
75.
Esposito Francesco Memoli Valeria Panico Speranza Claudia Trifuoggi Marco Di Natale Gabriella Maisto Giulia 《Plant and Soil》2019,436(1-2):517-526
Plant and Soil - The aims of this research were: i) to compare Cr, Cu, Ni and Pb concentrations in Quercus ilex L. leaves collected at urban/industrial and urban areas; ii) to investigate the main... 相似文献
76.
77.
Van Den Herrewegen Yana Denewet Lissa Buckinx An Albertini Giulia Van Eeckhaut Ann Smolders Ilse De Bundel Dimitri 《Neurochemical research》2019,44(3):600-608
Neurochemical Research - Temporal lobe epilepsy (TLE) is an acquired form of focal epilepsy, in which patients not only suffer from unprovoked, devastating seizures, but also from severe... 相似文献
78.
Soddu G Sanjust E Murgia S Rescigno A 《Pigment cell research / sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society》2004,17(2):135-141
Melanin (eumelanin) is commonly produced in mammals starting from tyrosine and/or 3,4-dioxyphenylalanine (DOPA) under the action of tyrosinase. 3-Hydroxyanthranilic acid and 3-hydroxykynurenine are intermediates occurring in the kynurenine pathway of tryptophan catabolism. In this paper, we show that these substances can interfere in melanin formation in vitro when tyrosine or DOPA is oxidized by molecular oxygen under catalysis by tyrosinase. In particular, when 3-hydroxyanthranilic acid is present, a brown and apparently water-soluble pigment is formed, whereas the typical eumelanin granules seem to become more and more rare as the concentration of 3-hydroxyanthranilic acid increases. Also in the presence of the latter, the rate of tyrosine and/or DOPA consumption decreases. A very complicated (13)C-NMR spectrum indicates the high complexity of the reaction. This involves both the true melanin precursor(s) and the tryptophan metabolite, even if with peculiar mechanism and kinetics. When 3-hydroxykynurenine is substituted for 3-hydroxyanthranilic acid the reaction leads to reddish pigments whereas xanthommatins (the typical oxidation products of 3-hydroxykynurenine) are absent. A possible relationship between some dischromic pathologies and tryptophan metabolic disorders is suggested. 相似文献
79.
Gianantonio?Battistuzzi Marco?Borsari Giulia?Di?Rocco Antonio?Ranieri Marco?SolaEmail author 《Journal of biological inorganic chemistry》2004,9(1):23-26
Compensation phenomena between the enthalpy and entropy changes of the reduction reaction for all classes of electron transport metalloproteins, namely cytochromes, iron-sulfur, and blue copper proteins, are brought to light. This is the first comprehensive report on such effects for biological redox reactions. Following Grunwalds approach for the interpretation of H/S compensation for solution reactions, it is concluded that reduction-induced solvent reorganization effects involving the hydration shell of the molecule dominate the reduction thermodynamics in these species, although they have no net effect on the E° values, owing to exact compensation. Thus the reduction potentials of these species are primarily determined by the selective enthalpic stabilization of one of the two oxidation states due to ligand binding interactions and electrostatics at the metal site and by the entropic effects of reduction-induced changes in protein flexibility. 相似文献
80.
Ilaria?Bartalesi Ivano?BertiniEmail author Giulia?Di?Rocco Antonio?Ranieri Antonio?Rosato Murugendra?Vanarotti Paul?R.?Vasos Maria?Silvia?Viezzoli 《Journal of biological inorganic chemistry》2004,9(5):600-608
The minimal mono-heme ferricytochrome
c from Bacillus pasteurii, containing 71 amino acids, has been further investigated through mutagenesis of different positions in the loop containing the iron ligand Met71. These mutations have been designed to sample different aspects of the loop structure, in order to obtain insights into the determinants of the stability of the iron(III) environment. In particular, positions 68, 72 and 75 have been essayed. Gln68 has been mutated to Lys to provide a suitable alternate ligand that can displace Met71 under denaturing conditions. Pro72 has been mutated to Gly and Ala to modify the range of allowed backbone conformations. Ile75, which is in van der Waals contact with Met71 and partly shields a long-lived water molecule in a protein cavity, has been substituted by Val and Ala to affect the network of inter-residue interactions around the metal site. The different contributions of the above amino acids to protein parameters such as structure, redox potential and the overall stability against unfolding with guanidinium hydrochloride are analyzed. While the structure remains essentially the same, the stability decreases with mutations. The comparison with mitochondrial c-type cytochromes is instructive.Abbreviations Bpcytc
soluble fragment of cytochrome c553 from Bacillus pasteurii
- GdmCl
guanidinium chloride
- I75A
Ile75 to Ala mutant
- I75V
Ile75 to Val mutant
- P72A
Pro72 to Ala mutant
- P72G
Pro72 to Gly mutant
- Q68K
Gln75 to Lys mutant
- WT
wild type 相似文献