全文获取类型
收费全文 | 234篇 |
免费 | 13篇 |
出版年
2023年 | 3篇 |
2022年 | 2篇 |
2021年 | 5篇 |
2020年 | 6篇 |
2019年 | 7篇 |
2018年 | 6篇 |
2017年 | 5篇 |
2016年 | 11篇 |
2015年 | 21篇 |
2014年 | 14篇 |
2013年 | 14篇 |
2012年 | 20篇 |
2011年 | 23篇 |
2010年 | 15篇 |
2009年 | 17篇 |
2008年 | 17篇 |
2007年 | 12篇 |
2006年 | 6篇 |
2005年 | 10篇 |
2004年 | 9篇 |
2003年 | 5篇 |
2002年 | 8篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1993年 | 1篇 |
1992年 | 1篇 |
排序方式: 共有247条查询结果,搜索用时 15 毫秒
171.
Marina Yu. Skorkina Evgenia A. Sladkova Elena A. Shamray Olga V. Cherkashina Maxim P. Evstigneev Anatoly S. Buchelnikov Yuriy I. Prylutskyy Uwe Ritter 《European biophysics journal : EBJ》2015,44(6):493-498
The influence of aqueous solution of pristine C60 fullerene (C60FAS) on functional activity of lymphocytes from a healthy person was studied for the first time. By means of atomic force microscopy, it was found that C60FAS in a concentration of 0.1 mg/ml increases the stiffness of the lymphocyte membrane by 41 % (p < 0.05) and lowers the functional activity of the plasmalemma surface, thereby constraining the use of its membrane material in physiological reactions using a hypotonic model in vitro. However, a cell retains the ability to regulate its volume and demonstrates relative resistance to hypo-osmotic stress. The resistance of lymphocytes in hypo-osmotic medium is facilitated by activation of the nucleus by C60 fullerene particles, which regulates the implementation of two consistent phases of an increase and decrease of cell volume, thereby retaining cell viability. All these indicate the impact of C60 fullerene on the cellular nucleus. 相似文献
172.
Eugene?G. Maksimov Evgeny?A. Shirshin Nikolai?N. Sluchanko Dmitry?V. Zlenko Evgenia?Y. Parshina Georgy?V. Tsoraev Konstantin?E. Klementiev Gleb?S. Budylin Franz-Josef Schmitt Thomas Friedrich Victor?V. Fadeev Vladimir?Z. Paschenko Andrew?B. Rubin 《Biophysical journal》2015,109(3):595-607
Orange carotenoid protein (OCP) is the photoactive protein that is responsible for high light tolerance in cyanobacteria. We studied the kinetics of the OCP photocycle by monitoring changes in its absorption spectrum, intrinsic fluorescence, and fluorescence of the Nile red dye bound to OCP. It was demonstrated that all of these three methods provide the same kinetic parameters of the photocycle, namely, the kinetics of OCP relaxation in darkness was biexponential with a ratio of two components equal to 2:1 independently of temperature. Whereas the changes of the absorption spectrum of OCP characterize the geometry and environment of its chromophore, the intrinsic fluorescence of OCP reveals changes in its tertiary structure, and the fluorescence properties of Nile red indicate the exposure of hydrophobic surface areas of OCP to the solvent following the photocycle. The results of molecular-dynamics studies indicated the presence of two metastable conformations of 3′-hydroxyechinenone, which is consistent with characteristic changes in the Raman spectra. We conclude that rotation of the β-ionylidene ring in the C-terminal domain of OCP could be one of the first conformational rearrangements that occur during photoactivation. The obtained results suggest that the photoactivated form of OCP represents a molten globule-like state that is characterized by increased mobility of tertiary structure elements and solvent accessibility. 相似文献
173.
Nathan Lawlor Eladio J. Márquez Peter Orchard Narisu Narisu Muhammad Saad Shamim Asa Thibodeau Arushi Varshney Romy Kursawe Michael R. Erdos Matt Kanke Huiya Gu Evgenia Pak Amalia Dutra Sheikh Russell Xingwang Li Emaly Piecuch Oscar Luo Peter S. Chines Michael L. Stitzel 《Cell reports》2019,26(3):788-801.e6
174.
Jenni Inkinen Merja Ahonen Evgenia Iakovleva Pasi Karppinen Eelis Mielonen Riika Mkinen Katriina Mannonen Juha Koivisto 《Journal of biophotonics》2020,13(1)
Organic dirt on touch surfaces can be biological contaminants (microbes) or nutrients for those but is often invisible by the human eye causing challenges for evaluating the need for cleaning. Using hyperspectral scanning algorithm, touch surface cleanliness monitoring by optical imaging was studied in a real‐life hospital environment. As the highlight, a human eye invisible stain from a dirty chair armrest was revealed manually with algorithms including threshold levels for intensity and clustering analysis with two excitation lights (green and red) and one bandpass filter (wavelength λ = 500 nm). The same result was confirmed by automatic k‐means clustering analysis from the entire dirty data of visible light (red, green and blue) and filters 420 to 720 nm with 20 nm increments. Overall, the collected touch surface samples (N = 156) indicated the need for cleaning in some locations by the high culturable bacteria and adenosine triphosphate counts despite the lack of visible dirt. Examples of such locations were toilet door lock knobs and busy registration desk armchairs. Thus, the studied optical imaging system utilizing the safe visible light area shows a promising method for touch surface cleanliness evaluation in real‐life environments. 相似文献
175.
Victoria E. Cotero Simon Y. Kimm Tiberiu M. Siclovan Rong Zhang Evgenia M. Kim Kazuhiro Matsumoto Tatsuo Gondo Peter T. Scardino Siavash Yazdanfar Vincent P. Laudone Cristina A. Tan Hehir 《PloS one》2015,10(6)
The ability to visualize and spare nerves during surgery is critical for avoiding chronic morbidity, pain, and loss of function. Visualization of such critical anatomic structures is even more challenging during minimal access procedures because the small incisions limit visibility. In this study, we focus on improving imaging of nerves through the use of a new small molecule fluorophore, GE3126, used in conjunction with our dual-mode (color and fluorescence) laparoscopic imaging instrument. GE3126 has higher aqueous solubility, improved pharmacokinetics, and reduced non-specific adipose tissue fluorescence compared to previous myelin-binding fluorophores. Dosing and kinetics were initially optimized in mice. A non-clinical modified Irwin study in rats, performed to assess the potential of GE3126 to induce nervous system injuries, showed the absence of major adverse reactions. Real-time intraoperative imaging was performed in a porcine model. Compared to white light imaging, nerve visibility was enhanced under fluorescence guidance, especially for small diameter nerves obscured by fascia, blood vessels, or adipose tissue. In the porcine model, nerve visualization was observed rapidly, within 5 to 10 minutes post-intravenous injection and the nerve fluorescence signal was maintained for up to 80 minutes. The use of GE3126, coupled with practical implementation of an imaging instrument may be an important step forward in preventing nerve damage in the operating room. 相似文献
176.
177.
Ekaterina A Alyamkina Valeriy P Nikolin Nelly A Popova Evgenia V Dolgova Anastasia S Proskurina Konstantin E Orishchenko Yaroslav R Efremov Elena R Chernykh Alexandr A Ostanin Sergey V Sidorov Dmitriy M Ponomarenko Stanislav N Zagrebelniy Sergey S Bogachev Mikhail A Shurdov 《Genetic vaccines and therapy》2010,8(1):1-10
Background
Immunization of mice with tumor homogenate after combined treatment with cyclophosphamide (CP) and double-stranded DNA (dsDNA) preparation is effective at inhibition of growth of tumor challenged after the treatment. It was assumed that this inhibition might be due to activation of the antigen-presenting cells. The purpose was to develop improved antitumor strategy using mice. We studied the combined action of cytostatics doxorubicin (Dox) plus CP with subsequent dsDNA preparation on tumor growth.Methods
Three-month old CBA/Lac mice were used in the experiments. Mice were injected with CP and human dsDNA preparation. The percentage of mature dendritic cells (DCs) was estimated by staining of mononuclear cells isolated from spleen and bone marrow 3, 6, and 9 days later with monoclonal antibodies CD34, CD80, and CD86. In the next set of experiments, mice were given intramuscularly injections of 1-3 × 105 tumor cells. Four days later, they were injected intravenously with 6-6.7 mg/kg Dox and intraperitoneally with 100-200 mg/kg CP; 200 mkg human DNA was injected intraperitoneally after CP administration. Differences in tumor size between groups were analyzed for statistical significance by Student's t-test. The MTT-test was done to determine the cytotoxic index of mouse leucocytes from treated groups.Results
The conducted experiments showed that combined treatment with CP and dsDNA preparation produce an increase in the total amount of mature DCs in vivo. Treatment of tumor bearers with preparation of fragmented dsDNA on the background of pretreatment with Dox plus CP demonstrated a strong suppression of tumor growth in two models. RLS, a weakly immunogenic, resistant to alkalyting cytostatics tumor, grew 3.4-fold slower when compared with the control (p < 0.001). In experiment with Krebs-2 tumor, only 2 of the 10 mice in the Dox+CP+DNA group had a palpable tumor on day 16. The cytotoxic index of leucocytes was 86.5% in the Dox+CP+DNA group, but it was 0% in the Dox+CP group.Conclusions
Thus, the set of experiments we performed showed that exogenous dsDNA, when administered on the background of pretreatment with Dox plus CP, has an antitumor effect possibly due to DC activation. 相似文献178.
Danielle G Lemay David J Lynn William F Martin Margaret C Neville Theresa M Casey Gonzalo Rincon Evgenia V Kriventseva Wesley C Barris Angie S Hinrichs Adrian J Molenaar Katherine S Pollard Nauman J Maqbool Kuljeet Singh Regan Murney Evgeny M Zdobnov Ross L Tellam Juan F Medrano J Bruce German Monique Rijnkels 《Genome biology》2009,10(4):1-18
One of the major genomics challenges is to better understand how correct gene expression is orchestrated. Recent studies have shown how spatial chromatin organization is critical in the regulation of gene expression. Here, we developed a suite of computer programs to identify chromatin conformation signatures with 5C technology http://Dostielab.biochem.mcgill.ca. We identified dynamic HoxA cluster chromatin conformation signatures associated with cellular differentiation. Genome-wide chromatin conformation signature identification might uniquely identify disease-associated states and represent an entirely novel class of human disease biomarkers. 相似文献
179.
180.
Davide Vigetti Anna Genasetti Evgenia Karousou Manuela Viola Paola Moretto Moira Clerici Sara Deleonibus Giancarlo De Luca Vincent C. Hascall Alberto Passi 《The Journal of biological chemistry》2010,285(32):24639-24645
Chronic inflammation is now accepted to have a critical role in the onset of several diseases as well as in vascular pathology, where macrophage transformation into foam cells contributes in atherosclerotic plaque formation. Endothelial cells (EC) have a critical function in recruitment of immune cells, and proinflammatory cytokines drive the specific expression of several adhesion proteins. During inflammatory responses several cells produce hyaluronan matrices that promote monocyte/macrophage adhesion through interactions with the hyaluronan receptor CD44 present on inflammatory cell surfaces. In this study, we used human umbilical chord vein endothelial cells (HUVECs) as a model to study the mechanism that regulates hyaluronan synthesis after treatment with proinflammatory cytokines. We found that interleukin 1β and tumor necrosis factors α and β, but not transforming growth factors α and β, strongly induced HA synthesis by NF-κB pathway. This signaling pathway mediated hyaluronan synthase 2 (HAS2) mRNA expression without altering other glycosaminoglycan metabolism. Moreover, we verified that U937 monocyte adhesion on stimulated HUVECs depends strongly on hyaluronan, and transfection with short interference RNA of HAS2 abrogates hyaluronan synthesis revealing the critical role of HAS2 in this process. 相似文献