全文获取类型
收费全文 | 439篇 |
免费 | 21篇 |
出版年
2023年 | 1篇 |
2022年 | 5篇 |
2021年 | 18篇 |
2020年 | 5篇 |
2019年 | 9篇 |
2018年 | 9篇 |
2017年 | 3篇 |
2016年 | 19篇 |
2015年 | 27篇 |
2014年 | 18篇 |
2013年 | 28篇 |
2012年 | 35篇 |
2011年 | 47篇 |
2010年 | 21篇 |
2009年 | 20篇 |
2008年 | 15篇 |
2007年 | 40篇 |
2006年 | 22篇 |
2005年 | 32篇 |
2004年 | 19篇 |
2003年 | 22篇 |
2002年 | 13篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1999年 | 4篇 |
1998年 | 7篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1994年 | 2篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1981年 | 2篇 |
1967年 | 1篇 |
排序方式: 共有460条查询结果,搜索用时 15 毫秒
101.
Rabot A Henry C Ben Baaziz K Mortreau E Azri W Lothier J Hamama L Boummaza R Leduc N Pelleschi-Travier S Le Gourrierec J Sakr S 《Plant & cell physiology》2012,53(6):1068-1082
Bud burst is a decisive process in plant architecture that requires light in Rosa sp. This light effect was correlated with stimulation of sugar transport and metabolism in favor of bud outgrowth. We investigated whether sugars could act as signaling entities in the light-mediated regulation of vacuolar invertases and bud burst. Full-length cDNAs encoding two vacuolar invertases (RhVI1 and RhVI2) were isolated from buds. Unlike RhVI2, RhVI1 was preferentially expressed in bursting buds, and was up-regulated in buds of beheaded plants exposed to light. To assess the importance of sugars in this process, the expression of RhVI1 and RhVI2 and the total vacuolar invertase activity were further characterized in buds cultured in vitro on 100 mM sucrose or mannitol under light or in darkness for 48 h. Unlike mannitol, sucrose promoted the stimulatory effect of light on both RhVI1 expression and vacuolar invertase activity. This up-regulation of RhVI1 was rapid (after 6 h incubation) and was induced by as little as 10 mM sucrose or fructose. No effect of glucose was found. Interestingly, both 30 mM palatinose (a non-metabolizable sucrose analog) and 5 mM psicose (a non-metabolizable fructose analog) promoted the light-induced expression of RhVI1 and total vacuolar invertase activity. Sucrose, fructose, palatinose and psicose all promoted bursting of in vitro cultured buds under light. These findings indicate that soluble sugars contribute to the light effect on bud burst and vacuolar invertases, and can function as signaling entities. 相似文献
102.
Kim W Essalmani R Szumska D Creemers JW Roebroek AJ D'Orleans-Juste P Bhattacharya S Seidah NG Prat A 《Molecular and cellular biology》2012,32(17):3382-3391
In mammals, seven proprotein convertases (PCs) cleave secretory proteins after basic residues, and four of them are called furin-like PCs: furin, PC5, PACE4, and PC7. In vitro, they share many substrates. However, furin is essential during development since deficient embryos die at embryonic day 11 and exhibit multiple developmental defects, particularly defects related to the function of endothelial cells. To define the role of furin in endothelial cells, an endothelial cell-specific knockout (ecKO) of the Furin gene was generated. Newborns die shortly after birth, indicating that furin is essential in these cells. Magnetic resonance imaging revealed that ecKO embryos exhibit ventricular septal defects (VSD) and/or valve malformations. In addition, primary cultures of wild-type and ecKO lung endothelial cells revealed that ecKO cells are unable to grow. Growth was efficiently rescued by extracellular soluble furin. Analysis of the processing of precursors of endothelin-1 (ET-1), adrenomedullin (Adm), transforming growth factor β1 (TGF-β1), and bone morphogenetic protein 4 (BMP4) confirmed that ET-1, Adm, and TGF-β1 are in vivo substrates of endothelial furin. Mature ET-1 and BMP4 forms were reduced by ~90% in ecKO purified endothelial cells from lungs. 相似文献
103.
104.
Azarkan M Dibiani R Goormaghtigh E Raussens V Baeyens-Volant D 《Biochimica et biophysica acta》2006,1764(6):1063-1072
The papaya Kunitz-type trypsin inhibitor, a 24-kDa glycoprotein, was purified to homogeneity. The purified inhibitor stoichiometrically inhibits bovine trypsin in a 1:1 molar ratio. Circular dichroism and infrared spectroscopy analyses demonstrated that the inhibitor contains extensive beta-sheet structures. The inhibitor was found to retain its full inhibitory activity over a broad pH range (1.5-11.0) and temperature (up to 80 degrees C), besides being stable at very high concentrations of strong chemical denaturants (e.g., 5.5 M guanidine hydrochloride). The inhibitor retained its compact structure over the pH range analyzed as shown by 8-anilino-1-naphtalenesulfonic acid binding characteristics, excluding the formation of some relaxed or molten state. Exposure to 2.5 mM dithiothreitol for 120 min caused a 33% loss of the inhibitory activity, while a loss of 75% was obtained in the presence of 20 mM of dithiothreitol during the same time period. A complete loss of the inhibitory activity was observed after incubation with 50 mM dithiothreitol for 5 min. Incubation of the inhibitor with general proteases belonging to different families revealed its extraordinary resistance to proteolysis in comparison with the soybean trypsin inhibitor, the archetypal member of the Kunitz-type inhibitors family. The inhibitor also exhibited a remarkable resistance to proteolytic degradation against pepsin for at least a 24-h incubation period. Instead, the soybean inhibitor was completely degraded after 2 h incubation with this aspartic protease. All these data demonstrated the high stability of the papaya trypsin inhibitor. 相似文献
105.
Med Abderrahmane K. Sanhoury Med Taieb Ben Dhia Med Rachid Khaddar 《Inorganica chimica acta》2009,362(10):3763-3768
The synthesis, characterisation and solution behaviour of a series of octahedral complexes SnCl4·2L (L = R2NP(O)(OCH2CF3)2; R = Me (1); Et (2) or L = P(O)(OCH2Rf)3; Rf = CF3 (3); C2F5 (4)) are described. Complexes 1-4 were prepared from SnCl4 and 2 equiv. of the ligand, L, in anhydrous CH2Cl2 solution. The adducts have been characterised by multinuclear (1H, 31P and 119Sn) NMR, IR spectroscopy and elemental analysis. In dichloromethane solution, the NMR data showed the presence of a mixture of cis and trans isomers for 1 and 2 and only the cis isomer for 3 and 4. The difference could be interpreted in terms of the electronic effects of the substituents on the phosphorus atom of the ligand. In addition, the solution structure of the complexes studied by variable temperature 31P-{1H} and 1H NMR in the presence of excess ligand indicated that the ligand exchange on the cis isomer dominates the chemistry. The metal-ligand exchange barriers were estimated to be 13.38 and 11.39 kcal/mol for 1 and 3, respectively. The results are discussed and compared with those previously reported for the related hexamethylphosphoramide adduct, SnCl4·2HMPA. 相似文献
106.
107.
Thaís Leal-Silva Flaviane Vieira-Santos Fabrício Marcus Silva Oliveira Luiza de Lima Silva Padro Lucas Kraemer Pablo Hemanoel da Paixo Matias Camila de Almeida Lopes Ana Cristina Loiola Ruas Isabella Carvalho de Azevedo Denise Silva Nogueira Milene Alvarenga Rachid Marcelo Vidigal Caliari Remo Castro Russo Ricardo Toshio Fujiwara Lilian Lacerda Bueno 《PLoS neglected tropical diseases》2021,15(7)
Toxocariasis is a neglected disease that affects people around the world. Humans become infected by accidental ingestion of eggs containing Toxocara canis infective larvae, which upon reaching the intestine, hatch, penetrate the mucosa and migrate to various tissues such as liver, lungs and brain. Studies have indicated that Th2 response is the main immune defense mechanism against toxocariasis, however, there are still few studies related to this response, mainly the IL-33/ST2 pathway. Some studies have reported an increase in IL-33 during helminth infections, including T. canis. By binding to its ST2 receptor, IL-33 stimulating the Th2 polarized immune cell and cytokine responses. Thus, we aimed to investigate the role of the IL-33/ST2 pathway in the context of T. canis larval migration and the immunological and pathophysiological aspects of the infection in the liver, lungs and brain from Wild-Type (WT) BALB/c background and genetically deficient mice for the ST2 receptor (ST2-/-). The most important findings revealed that the IL-33/ST2 pathway is involved in eosinophilia, hepatic and cerebral parasitic burden, and induces the formation of granulomas related to tissue damage and pulmonary dysfunction. However, ST2-/- mice, the immune response was skewed to Th1/Th17 type than Th2, that enhanced the control of parasite burden related to IgG2a levels, tissue macrophages infiltration and reduced lung dysfunction. Collectively, our results demonstrate that the Th2 immune response triggered by IL-33/ST2 pathway mediates susceptibility to T. canis, related to parasitic burden, eosinophilia and granuloma formation in which consequently contributes to tissue inflammation and injury. 相似文献
108.
Caroline Smal Didier Vertommen Rachid Amsailale Angélique Arts Pierre Morsomme Eric Van Den Neste Françoise Bontemps 《Archives of biochemistry and biophysics》2010,502(1):44-52
Deoxycytidine kinase (dCK) is a key enzyme in the salvage of deoxynucleosides and in the activation of several anticancer and antiviral nucleoside analogues. We recently showed that dCK was activated in vivo by phosphorylation of Ser-74. However, the protein kinase responsible was not identified. Ser-74 is located downstream a Glu-rich region, presenting similarity with the consensus phosphorylation motif of casein kinase 1 (CKI), and particularly of CKI δ. We showed that recombinant CKI δ phosphorylated several residues of bacterially overexpressed dCK: Ser-74, but also Ser-11, Ser-15, and Thr-72. Phosphorylation of dCK by CKI δ correlated with increased activity reaching at least 4-fold. Site-directed mutagenesis demonstrated that only Ser-74 phosphorylation was involved in dCK activation by CKI δ, strengthening the key role of this residue in the control of dCK activity. However, neither CKI δ inhibitors nor CKI δ siRNA-mediated knock-down modified Ser-74 phosphorylation or dCK activity in cultured cells. Moreover, these approaches did not prevent dCK activation induced by treatments enhancing Ser-74 phosphorylation. Taken together, the data preclude a role of CKI δ in the regulation of dCK activity in vivo. Nevertheless, phosphorylation of dCK by CKI δ could be a useful tool for elucidating the influence of Ser-74 phosphorylation on the structure-activity relationships in the enzyme. 相似文献
109.
Rachid Ait-Haddou Yoshihisa Kurachi Taishin Nomura 《Journal of theoretical biology》2010,264(1):55-65
In intracellular calcium signaling, calcium buffers has been recognized for their role in reshaping and localizing the calcium concentration profile in the vicinity of the channel, as well as reducing the effective diffusion of free calcium. In the presence of an excess of endogenous or exogenous buffers, linearization of the reaction-diffusion system describing the calcium-buffer dynamics has been instrumental in understanding the extent of the microdomain formation and in quantifying the apparent diffusion of the free calcium. In these linearized models, the conclusions are usually drawn from the steady-state solutions upon the opening of the channel. In this work, using the joint Laplace-Fourier method, we give an explicit integral transient solution, as well as, the long-time asymptotic behavior of the linearized calcium-buffer dynamics. The results confirm and emphasize the long stated intuitions on the diffusive character of the calcium-buffer dynamics. Numerical validations of our analytical results will be discussed. 相似文献
110.