全文获取类型
收费全文 | 133篇 |
免费 | 6篇 |
出版年
2021年 | 1篇 |
2019年 | 1篇 |
2018年 | 1篇 |
2016年 | 3篇 |
2015年 | 3篇 |
2014年 | 8篇 |
2013年 | 6篇 |
2012年 | 10篇 |
2011年 | 8篇 |
2010年 | 9篇 |
2009年 | 4篇 |
2008年 | 5篇 |
2007年 | 5篇 |
2006年 | 4篇 |
2005年 | 4篇 |
2004年 | 4篇 |
2002年 | 6篇 |
2001年 | 8篇 |
1999年 | 3篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1994年 | 1篇 |
1993年 | 4篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1989年 | 5篇 |
1988年 | 1篇 |
1987年 | 3篇 |
1982年 | 2篇 |
1980年 | 1篇 |
1976年 | 1篇 |
1975年 | 3篇 |
1973年 | 2篇 |
1970年 | 2篇 |
1967年 | 2篇 |
1966年 | 2篇 |
1965年 | 1篇 |
1964年 | 4篇 |
1962年 | 2篇 |
1961年 | 1篇 |
排序方式: 共有139条查询结果,搜索用时 46 毫秒
51.
52.
53.
54.
Greffes de cornée automatisées par laser femtoseconde optimisé et système de contrôle aberrométrique
K. Plamann F. Aptel N. Château C. Crotti F. Deloison F. Druon P. Georges M. Hanna B. Lamory J.-M. Legeais X. Levecq F. Morin V. Nuzzo D.-A. Peyrot M. Savoldelli 《IRBM》2010,31(2):97-100
We present a first evaluation of the results of the GRECO project which aims to conceive and realise an innovative device for ocular surgery by ultrafast pulse laser optimised for corneal grafting. 相似文献
55.
Kristin LM Boylan Somaieh Afiuni-Zadeh Melissa A Geller Kayla Hickey Timothy J Griffin Stefan E Pambuccian Amy PN Skubitz 《Clinical proteomics》2014,11(1):30
Background
The proteomic analysis of body fluids is a growing technology for the identification of protein biomarkers of disease. Given that Papanicolaou tests (Pap tests) are routinely performed on over 30 million women annually in the U.S. to screen for cervical cancer, we examined the residual Pap test fluid as a source of protein for analysis by mass spectrometry (MS). In the liquid-based Pap test, cervical cells are collected from the ectocervix and placed into an alcohol-based fixative prior to staining and pathologic examination. We hypothesized that proteins shed by cells of the female genital tract can be detected in the Pap test fixative by MS-based proteomic techniques. We examined the feasibility of using residual fluid from discarded Pap tests with cytologically “normal” results to optimize sample preparation for MS analysis. The protein composition of the cell-free Pap test fluid was determined by silver staining of sodium dodecyl sulfate -polyacrylamide gels, and the abundance of serum proteins was examined by Western immunoblot using an antibody against human serum albumin. Both pooled and individual samples were trypsin digested and analyzed by two-dimensional MS/MS. Proteins were identified by searching against the Human Uniprot database, and characterized for localization, function and relative abundance.Results
The average volume of the residual Pap test fluid was 1.5 ml and the average protein concentration was 0.14 mg/ml. By Western immunoblot we showed that the amount of albumin in each sample was significantly reduced compared to normal serum. By MS/MS, we identified 714 unique proteins in pooled Pap test samples and an average of 431 proteins in individual samples. About 40% of the proteins identified were extracellular or localized to the plasma membrane. Almost 20% of the proteins identified were involved in immunity and defense, characteristic of the healthy cervical-vaginal proteome. By merging the protein sets from the individual and pooled Pap test samples, we created a “Normal Pap test Core Proteome” consisting of 153 proteins.Conclusions
Residual Pap test fluid contains a sufficient amount of protein for analysis by MS and represents a valuable biospecimen source for the identification of protein biomarkers for gynecological diseases. 相似文献56.
C Oliveira LM Vera JF López-Olmeda JM Guzmán E Ma?anós J Ramos FJ Sánchez-Vázquez 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2009,152(2):168-175
In this paper we attempted to investigate the existence of daily fluctuations on plasma sexual steroids (17beta-estradiol, E(2) and testosterone, T) in Senegal sole (Solea senegalensis) females. We described the monthly day/night concentrations and seasonal daily rhythms in animals reared under natural photo- and thermo-period. In addition, the influence of the natural annual fluctuation of the water temperature on the plasma concentration of these steroids was investigated, using one group of Senegal sole under a natural photoperiod, but with an attenuated thermal cycle (around 17-20 degrees C) for one year. Although no significant day/night differences were detected in monthly samplings, the existence of an annual rhythm of E(2) and T (p<0.01) with an acrophase in February was revealed by COSINOR analysis. Maximum values were reached in March for both steroids (6.1+/-1.7 ng mL(-1) at mid-dark, MD and 4.0+/-0.6 ng mL(-1) at mid-light, ML for E2 and 1.4+/-0.4 ng mL(-1) at MD and 0.8+/-0.1 ng mL(-1) at ML for T) in anticipation of the spawning season (May-June). As regards seasonal daily rhythms, the presence of daily oscillations was revealed. At the spring solstice (21st March) a daily rhythm was observed for both steroids (COSINOR, p<0.01), with an acrophase at 20:00 h (E(2)) and at 21:08 h (T). In summer, autumn and winter no daily rhythms were observed due to the low steroid levels at those seasons. When Senegal sole females were submitted to an attenuated annual thermal cycle, the steroid rhythm disappeared (there was no surge in spring, as in the control group) and these fish did not spawn, despite being subjected to natural photoperiod conditions. This result underlined the importance of the natural annual fluctuation of water temperature and photoperiod on the synchronization of the spawning season and on the onset of steroidogenesis. 相似文献
57.
Kristin LM Boylan John D Andersen Lorraine B Anderson LeeAnn Higgins Amy PN Skubitz 《Proteome science》2010,8(1):31
Background
Ovarian cancer is the most lethal gynecologic malignancy, with the majority of cases diagnosed at an advanced stage when treatments are less successful. Novel serum protein markers are needed to detect ovarian cancer in its earliest stage; when detected early, survival rates are over 90%. The identification of new serum biomarkers is hindered by the presence of a small number of highly abundant proteins that comprise approximately 95% of serum total protein. In this study, we used pooled serum depleted of the most highly abundant proteins to reduce the dynamic range of proteins, and thereby enhance the identification of serum biomarkers using the quantitative proteomic method iTRAQ®.Results
Medium and low abundance proteins from 6 serum pools of 10 patients each from women with serous ovarian carcinoma, and 6 non-cancer control pools were labeled with isobaric tags using iTRAQ® to determine the relative abundance of serum proteins identified by MS. A total of 220 unique proteins were identified and fourteen proteins were elevated in ovarian cancer compared to control serum pools, including several novel candidate ovarian cancer biomarkers: extracellular matrix protein-1, leucine-rich alpha-2 glycoprotein-1, lipopolysaccharide binding protein-1, and proteoglycan-4. Western immunoblotting validated the relative increases in serum protein levels for several of the proteins identified.Conclusions
This study provides the first analysis of immunodepleted serum in combination with iTRAQ® to measure relative protein expression in ovarian cancer patients for the pursuit of serum biomarkers. Several candidate biomarkers were identified which warrant further development.58.
Rappl C Barbier P Bourgarel-Rey V Grégoire C Gilli R Carre M Combes S Finet JP Peyrot V 《Biochemistry》2006,45(30):9210-9218
The synthesis of different 4-arylcoumarin analogues of combretastatin A-4 led to the identification of two new compounds (1 and 2) with potent cytotoxic activity on a CEM leukemia cell line and a third one completely inactive (compound 3). It was suggested that the cytotoxicity of compounds 1 and 2 may be related to their interaction with microtubules and tubulin, since these compounds inhibit microtubule formation from purified tubulin in vitro [Bailly et al. (2003) J. Med. Chem. 46 (25), 5437-5444]. In the present study, tubulin was identified as the main target of these molecules. We studied structure-activity relationships of these compounds using biological experiments specific for tubulin binding. The modification of cell cycle progression induced by compounds 1 and 2 was characterized by an apoptotic induction on human breast cells (HBL100). In addition, these two molecules disturbed cell survival by depolymerizing the microtubule network, leading to a mitotic block. We then determined the thermodynamic parameters of their interaction with purified tubulin by fluorescence spectroscopy and isothermal microcalorimetry. These results, together with a superimposition of the molecule on colchicine in the X-ray-determined three-dimensional structure model of tubulin-colchicine complex, allowed us to identify the pharmacophore of the combretastatin A-4 analogues responsible for their biological activity. 相似文献
59.
Bourdron J Commeiras L Barbier P Bourgarel-Rey V Pasquier E Vanthuyne N Hubaud JC Peyrot V Parrain JL 《Bioorganic & medicinal chemistry》2006,14(16):5540-5548
The synthesis of an analog of caulerpenyne having a trimethoxyaryl moiety was achieved in 11% overall yield over 11 steps. Its biological activity has been evaluated as inhibitor of in vitro tubulin polymerization or angiogenesis. 相似文献
60.
Pascale Barbier Audrey Dorléans Francois Devred Laura Sanz Diane Allegro Carlos Alfonso Marcel Knossow Vincent Peyrot Jose M. Andreu 《The Journal of biological chemistry》2010,285(41):31672-31681
Tubulin is able to switch between a straight microtubule-like structure and a curved structure in complex with the stathmin-like domain of the RB3 protein (T2RB3). GTP hydrolysis following microtubule assembly induces protofilament curvature and disassembly. The conformation of the labile tubulin heterodimers is unknown. One important question is whether free GDP-tubulin dimers are straightened by GTP binding or if GTP-tubulin is also curved and switches into a straight conformation upon assembly. We have obtained insight into the bending flexibility of tubulin by analyzing the interplay of tubulin-stathmin association with the binding of several small molecule inhibitors to the colchicine domain at the tubulin intradimer interface, combining structural and biochemical approaches. The crystal structures of T2RB3 complexes with the chiral R and S isomers of ethyl-5-amino-2-methyl-1,2-dihydro-3-phenylpyrido[3,4-b]pyrazin-7-yl-carbamate, show that their binding site overlaps with colchicine ring A and that both complexes have the same curvature as unliganded T2RB3. The binding of these ligands is incompatible with a straight tubulin structure in microtubules. Analytical ultracentrifugation and binding measurements show that tubulin-stathmin associations (T2RB3, T2Stath) and binding of ligands (R, S, TN-16, or the colchicine analogue MTC) are thermodynamically independent from one another, irrespective of tubulin being bound to GTP or GDP. The fact that the interfacial ligands bind equally well to tubulin dimers or stathmin complexes supports a bent conformation of the free tubulin dimers. It is tempting to speculate that stathmin evolved to recognize curved structures in unassembled and disassembling tubulin, thus regulating microtubule assembly. 相似文献