全文获取类型
收费全文 | 202篇 |
免费 | 6篇 |
出版年
2023年 | 2篇 |
2022年 | 2篇 |
2021年 | 4篇 |
2020年 | 5篇 |
2019年 | 3篇 |
2018年 | 8篇 |
2017年 | 4篇 |
2016年 | 7篇 |
2015年 | 13篇 |
2014年 | 12篇 |
2013年 | 14篇 |
2012年 | 18篇 |
2011年 | 14篇 |
2010年 | 3篇 |
2009年 | 7篇 |
2008年 | 16篇 |
2007年 | 13篇 |
2006年 | 11篇 |
2005年 | 13篇 |
2004年 | 11篇 |
2003年 | 5篇 |
2002年 | 7篇 |
2001年 | 2篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1995年 | 1篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1989年 | 1篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1970年 | 2篇 |
1967年 | 1篇 |
排序方式: 共有208条查询结果,搜索用时 328 毫秒
1.
B. Ringelhann J. G. Szelenyi M. Horanyi M. Svobodova V. Divoky K. Indrak S. Hollân A. Marosi M. Laub T. H. J. Huisman 《Human genetics》1993,92(4):385-387
We have identified seven different -thalassemia mutations and one -thalassemia determinant (the Sicilian type) in 32 members of 17 Hungarian families. The most common mutation is the IVS-I-1 (GA) change; its high frequency is comparable to that observed in neighboring Czechoslovakia. Additional mutations are of Mediterranean origin. One rare mutation (initiation codonATGGTG) was identified as an independent mutation because of the absence of known polymorphisms in the -globin gene. One new frameshift at codon 51 (-C) was observed in a single individual; hematological data were as expected for a °-thalassemia heterozygosity. 相似文献
2.
Júlia Domján Annamária Fricska Lajos Madarász Martin Gyürkés Ákos Köte Attila Farkas Panna Vass Csaba Fehér Balázs Horváth Kálmán Könczöl Hajnalka Pataki Zsombor Kristóf Nagy György János Marosi Edit Hirsch 《Biotechnology progress》2020,36(6):e3052
The use of Process Analytical Technology tools coupled with chemometrics has been shown great potential for better understanding and control of mammalian cell cultivations through real-time process monitoring. In-line Raman spectroscopy was utilized to determine the glucose concentration of the complex bioreactor culture medium ensuring real-time information for our process control system. This work demonstrates a simple and fast method to achieve a robust partial least squares calibration model under laboratory conditions in an early phase of the development utilizing shake flask and bioreactor cultures. Two types of dynamic feeding strategies were accomplished where the multi-component feed medium additions were controlled manually and automatically based on the Raman monitored glucose concentration. The impact of these dynamic feedings was also investigated and compared to the traditional bolus feeding strategy on cellular metabolism, cell growth, productivity, and binding activity of the antibody product. Both manual and automated dynamic feeding strategies were successfully applied to maintain the glucose concentration within a narrower and lower concentration range. Thus, besides glucose, the glutamate was also limited at low level leading to reduced production of inhibitory metabolites, such as lactate and ammonia. Consequently, these feeding control strategies enabled to provide beneficial cultivation environment for the cells. In both experiments, higher cell growth and prolonged viable cell cultivation were achieved which in turn led to increased antibody product concentration compared to the reference bolus feeding cultivation. 相似文献
3.
Csilla Stenger‐Kovcs Edina Lengyel Krisztina Buczk Judit Padisk Jnos Korponai 《Ecology and evolution》2020,10(1):320-335
Saline lakes, among the most seriously endangered ecosystems, are threatened due to climate change and human activities. One valuable feature of these environments is that they constitute areas of high biodiversity. Ecologists are, therefore, under great pressure to improve their understanding of the effects of natural and anthropogenic disturbances on the biodiversity of saline lakes. In this study, a total of 257 samples from 32 soda pans in Central Europe between 2006 and 2015 were examined. The effects of environmental variables and of geographical and limnoecological factors on functional diversity were analyzed. Furthermore, the explanatory power of the trait‐based approach was assessed, and the applicability of the indices for biomonitoring purposes was determined. It was found that low habitat heterogeneity and harsh environments lead to the selection of a small number of suitable traits, and consequently, to a naturally low level of functional diversity. Anthropogenic activities enhance diversity at functional level due to the shift toward freshwater characteristics. On the regional scale, the effects of the region and status (natural, degraded, reconstructed) on diatom functional diversity were significant and more pronounced than that of the environmental and other limnoecological factors. The degree of variance found in functional diversity ascribed to environmental variables is five times greater in the case of the application of a trait‐based approach, than when a taxonomic one is employed in the literature. Each of the tested functional diversity indices was sensitive to the most important environmental variables. Furthermore, these were type‐specific and proved to be more complex indicators than taxonomic metrics. It is possible to suggest four functional diversity indices (FGR, FRic, FDis, and FDiv) which emphasize their independence from substrate and seasonal variations for ecological status assessment and conservation planning. 相似文献
4.
Csilla Ferencz Pál Petrovszki Zoltán Kóta Elfrieda Fodor-Ayaydin Lajos Haracska Attila Bóta Zoltán Varga András Dér Derek Marsh Tibor Páli 《European biophysics journal : EBJ》2013,42(2-3):147-158
The rate of rotation of the rotor in the yeast vacuolar proton-ATPase (V-ATPase), relative to the stator or steady parts of the enzyme, is estimated in native vacuolar membrane vesicles from Saccharomyces cerevisiae under standardised conditions. Membrane vesicles are formed spontaneously after exposing purified yeast vacuoles to osmotic shock. The fraction of total ATPase activity originating from the V-ATPase is determined by using the potent and specific inhibitor of the enzyme, concanamycin A. Inorganic phosphate liberated from ATP in the vacuolar membrane vesicle system, during ten min of ATPase activity at 20 °C, is assayed spectrophotometrically for different concanamycin A concentrations. A fit of the quadratic binding equation, assuming a single concanamycin A binding site on a monomeric V-ATPase (our data are incompatible with models assuming multiple binding sites), to the inhibitor titration curve determines the concentration of the enzyme. Combining this with the known ATP/rotation stoichiometry of the V-ATPase and the assayed concentration of inorganic phosphate liberated by the V-ATPase, leads to an average rate of ~10 Hz for full 360° rotation (and a range of 6–32 Hz, considering the ± standard deviation of the enzyme concentration), which, from the time-dependence of the activity, extrapolates to ~14 Hz (8–48 Hz) at the beginning of the reaction. These are lower-limit estimates. To our knowledge, this is the first report of the rotation rate in a V-ATPase that is not subjected to genetic or chemical modification and is not fixed to a solid support; instead it is functioning in its native membrane environment. 相似文献
5.
Introduction
Abnormal cancer metabolism creates a glycolytic-dependency which can be exploited by lowering glucose availability to the tumor. The ketogenic diet (KD) is a low carbohydrate, high fat diet which decreases blood glucose and elevates blood ketones and has been shown to slow cancer progression in animals and humans. Abnormal tumor vasculature creates hypoxic pockets which promote cancer progression and further increase the glycolytic-dependency of cancers. Hyperbaric oxygen therapy (HBO2T) saturates tumors with oxygen, reversing the cancer promoting effects of tumor hypoxia. Since these non-toxic therapies exploit overlapping metabolic deficiencies of cancer, we tested their combined effects on cancer progression in a natural model of metastatic disease.Methods
We used the firefly luciferase-tagged VM-M3 mouse model of metastatic cancer to compare tumor progression and survival in mice fed standard or KD ad libitum with or without HBO2T (2.5 ATM absolute, 90 min, 3x/week). Tumor growth was monitored by in vivo bioluminescent imaging.Results
KD alone significantly decreased blood glucose, slowed tumor growth, and increased mean survival time by 56.7% in mice with systemic metastatic cancer. While HBO2T alone did not influence cancer progression, combining the KD with HBO2T elicited a significant decrease in blood glucose, tumor growth rate, and 77.9% increase in mean survival time compared to controls.Conclusions
KD and HBO2T produce significant anti-cancer effects when combined in a natural model of systemic metastatic cancer. Our evidence suggests that these therapies should be further investigated as potential non-toxic treatments or adjuvant therapies to standard care for patients with systemic metastatic disease. 相似文献6.
Anna Sophie Berghoff Thomas Spanberger Aysegül Ilhan-Mutlu Manuel Magerle Markus Hutterer Adelheid Woehrer Monika Hackl Georg Widhalm Karin Dieckmann Christine Marosi Peter Birner Daniela Prayer Matthias Preusser 《PloS one》2013,8(2)
Background
MRI-based diffusion-weighted imaging (DWI) visualizes the local differences in water diffusion in vivo. The prognostic value of DWI signal intensities on the source images and apparent diffusion coefficient (ADC) maps respectively has not yet been studied in brain metastases (BM).Methods
We included into this retrospective analysis all patients operated for single BM at our institution between 2002 and 2010, in whom presurgical DWI and BM tissue samples were available. We recorded relevant clinical data, assessed DWI signal intensity and apparent diffusion coefficient (ADC) values and performed histopathological analysis of BM tissues. Statistical analyses including uni- and multivariate survival analyses were performed.Results
65 patients (34 female, 31 male) with a median overall survival time (OS) of 15 months (range 0–99 months) were available for this study. 19 (29.2%) patients presented with hyper-, 3 (4.6%) with iso-, and 43 (66.2%) with hypointense DWI. ADCmean values could be determined in 32 (49.2%) patients, ranged from 456.4 to 1691.8*10−6 mm2/s (median 969.5) and showed a highly significant correlation with DWI signal intensity. DWI hyperintensity correlated significantly with high amount of interstitial reticulin deposition. In univariate analysis, patients with hyperintense DWI (5 months) and low ADCmean values (7 months) had significantly worse OS than patients with iso/hypointense DWI (16 months) and high ADCmean values (30 months), respectively. In multivariate survival analysis, high ADCmean values retained independent statistical significance.Conclusions
Preoperative DWI findings strongly and independently correlate with OS in patients operated for single BM and are related to interstitial fibrosis. Inclusion of DWI parameters into established risk stratification scores for BM patients should be considered. 相似文献7.
Judit Molnár Csilla Fazakas János Haskó Orsolya Sipos Krisztina Nagy Ádám Nyúl-Tóth 《Cell Adhesion & Migration》2016,10(3):269-281
Brain metastases are common and devastating complications of both breast cancer and melanoma. Although mammary carcinoma brain metastases are more frequent than those originating from melanoma, this latter has the highest tropism to the brain. Using static and dynamic in vitro approaches, here we show that melanoma cells have increased adhesion to the brain endothelium in comparison to breast cancer cells. Moreover, melanoma cells can transmigrate more rapidly and in a higher number through brain endothelial monolayers than breast cancer cells. In addition, melanoma cells have increased ability to impair tight junctions of cerebral endothelial cells. We also show that inhibition of Rac or PI3K impedes adhesion of breast cancer cells and melanoma cells to the brain endothelium. In addition, inhibition of Rac or PI3K inhibits the late phase of transmigration of breast cancer cells and the early phase of transmigration of melanoma cells. On the other hand, the Rac inhibitor EHT1864 impairs the junctional integrity of the brain endothelium, while the PI3K inhibitor LY294002 has no damaging effect on interendothelial junctions. We suggest that targeting the PI3K/Akt pathway may represent a novel opportunity in preventing the formation of brain metastases of melanoma and breast cancer. 相似文献
8.
Edit Hirsch Hajnalka Pataki Júlia Domján Attila Farkas Panna Vass Csaba Fehér Zsolt Barta Zsombor K. Nagy György J. Marosi István Csontos 《Biotechnology progress》2019,35(5):e2848
Raman spectroscopy as a process analytical technology tool was implemented for the monitoring and control of ethanol fermentation carried out with Saccharomyces cerevisiae. The need for the optimization of bioprocesses such as ethanol production, to increase product yield, enhanced the development of control strategies. The control system developed by the authors utilized noninvasive Raman measurements to avoid possible sterilization problems. Real-time data analysis was applied using partial least squares regression (PLS) method. With the aid of spectral pretreatment and multivariate data analysis, the monitoring of glucose and ethanol concentration was successful during yeast fermentation with the prediction error of 4.42 g/L for glucose and 2.40 g/L for ethanol. By Raman spectroscopy-based feedback control, the glucose concentration was maintained at 100 g/L by the automatic feeding of concentrated glucose solution. The control of glucose concentration during fed-batch fermentation resulted in increased ethanol production. Ethanol yield of 86% was achieved compared to the batch fermentation when 75 % yield was obtained. The results show that the use of Raman spectroscopy for the monitoring and control of yeast fermentation is a promising way to enhance process understanding and achieve consistently high production yield. 相似文献
9.
Dombroski MA Letavic MA McClure KF Barberia JT Carty TJ Cortina SR Csiki C Dipesa AJ Elliott NC Gabel CA Jordan CK Labasi JM Martin WH Peese KM Stock IA Svensson L Sweeney FJ Yu CH 《Bioorganic & medicinal chemistry letters》2004,14(4):919-923
The synthesis and in vitro p38 alpha activity of a novel series of benzimidazolone inhibitors is described. The p38 alpha SAR is consistent with a mode of binding wherein the benzimidazolone carbonyl serves as the H-bond acceptor to Met109 of p38 alpha in a manner analogous to the pyridine nitrogen of prototypical pyridylimidazole p38 inhibitors. Potent p38 alpha activity comparable to that of several previously reported p38 inhibitors is observed for this novel chemotype. 相似文献
10.