首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   398篇
  免费   4篇
化学   322篇
晶体学   9篇
力学   8篇
数学   22篇
物理学   41篇
  2023年   1篇
  2022年   21篇
  2021年   30篇
  2020年   9篇
  2019年   6篇
  2018年   3篇
  2017年   8篇
  2016年   11篇
  2015年   11篇
  2014年   10篇
  2013年   27篇
  2012年   19篇
  2011年   22篇
  2010年   19篇
  2009年   18篇
  2008年   25篇
  2007年   22篇
  2006年   26篇
  2005年   22篇
  2004年   16篇
  2003年   12篇
  2002年   17篇
  2001年   16篇
  2000年   2篇
  1999年   1篇
  1998年   3篇
  1997年   3篇
  1995年   1篇
  1994年   2篇
  1993年   1篇
  1992年   2篇
  1991年   2篇
  1990年   3篇
  1987年   1篇
  1986年   2篇
  1985年   1篇
  1984年   2篇
  1983年   1篇
  1981年   1篇
  1978年   1篇
  1975年   1篇
  1968年   1篇
排序方式: 共有402条查询结果,搜索用时 31 毫秒
321.
New isopropylated fused azaisocytosine-containing congeners (I–VI) have previously been reported as promising anticancer drug candidates, so further research on these molecules in the preclinical development phase is fully justified and necessary. For this reason, in the present paper, we assess the toxicity/safety profiles of all the compounds using Danio rerio and red blood cell models, and examine the effect of the most selective congeners on the activation of apoptotic caspases in cancer and normal cells. In order to evaluate the effect of each molecule on the development of zebrafish embryos/larvae and to select the safest compounds for further study, various phenotypic parameters (i.e., mortality, hatchability, heart rate, heart oedema, yolk sac utilization, swim bladder development and body shape) were observed, and the half maximal lethal concentration, the maximal non-lethal concentration and no observed adverse effect concentration for each compound were established. The effect of all the isopropylated molecules was compared to that of an anticancer agent pemetrexed. The lipophilicity-dependent structure–toxicity correlations were also determined. To establish the possible interaction of the compounds with red blood cells, an ex vivo hemolysis test was performed. It was shown that almost all of the investigated isopropylated congeners have no adverse phenotypic effect on zebrafish development during five-day exposure at concentrations up to 50 μM (I–III) or up to 20 μM (IV–V), and that they are less toxic for embryos/larvae than pemetrexed, demonstrating their safety. At the same time, all the molecules did not adversely affect the red blood cells, which confirms their very good hemocompatibility. Moreover, they proved to be activators of apoptotic caspases, as they increased caspase-3, -7 and -9 levels in human breast carcinoma cells. The conducted research allows us to select—from among the anticancer active drug candidates—compounds that are safe for developing zebrafish and red blood cells, suitable for further in vivo pharmacological tests.  相似文献   
322.
Fungal laccase obtained from a Cerrena unicolor strain was used as an effective biocatalyst for the transformation of 8-anilino-1-naphthalenesulfonic acid into a green-coloured antibacterial compound, which can be considered as both an antimicrobial agent and a textile dye, simultaneously. The process of biosynthesis was performed in buffered solutions containing methanol as a co-solvent, allowing better solubilisation of substrate. The transformation process was optimised in terms of the buffer pH value, laccase activity, and concentrations of the substrate and co-solvent. The crude product obtained exhibited low cytotoxicity, antibacterial properties against Staphylococcus aureus and Staphylococcus epidermidis, and antioxidant properties. Moreover, the synthesised green-coloured compound proved non-allergenic and demonstrated a high efficiency of dyeing wool fibres.  相似文献   
323.
A thorough understanding of cancer pathogenesis is a necessary step in the development of more effective and safer therapy. However, due to the complexity of the process and intricate interactions, studying tumor development is an extremely difficult and challenging task. In bringing this issue closer, different scientific models with various advancement levels are helpful. Cell cultures is a system that is too simple and does not allow for multidirectional research. On the other hand, rodent models, although commonly used, are burdened with several limitations. For this reason, new model organisms that will allow for the studying of carcinogenesis stages and factors reliably involved in them are urgently sought after. Danio rerio, an inconspicuous fish endowed with unique features, is gaining in importance in the world of scientific research. Including it in oncological research brings solutions to many challenges afflicting modern medicine. This article aims to illustrate the usefulness of Danio rerio as a model organism which turns out to be a powerful and unique tool for studying the stages of carcinogenesis and solving the hitherto incomprehensible processes that lead to the development of the disease.  相似文献   
324.

Titanium oxide nanoparticles modified with D-(+)-mannose were obtained. In the process of their formation, they were conjugated with an active substance (tadalafil). The physicochemical properties of the obtained products were assessed, and the size and electrokinetic potential were determined using a dynamic light scattering technique. X-ray diffractometry was applied in order to define the crystalline properties, and Fourier-transform infrared spectroscopy was used to confirm the formation of the desired products. It was possible to obtain TiO2 coated with D-(+)-mannose. The average size of nanoparticles was between 230 and 268 nm. The release of the active substance from the product over a time period of three hours was assessed against the reference material, which was not modified by D-(+)-mannose. The results indicate that covering titanium oxide nanoparticles with the modifying substance favours a slower rate of release for the active substance, which is the desired effect from a pharmacological point of view. The releasing of active substance from modified products was even 68% slower than that from the reference product. These modified titanium oxides are promising materials that may have found an application as drug carriers.

Graphic Abstract
  相似文献   
325.
The visible trend in the development of the snack market focuses on the use of innovative technologies such as low-temperature or hybrid processes that allow the preservation of native ingredients of raw plant materials. In addition, the high antioxidant potential of, for example, chokeberry fruit can be used to support technological processes and create new products. The aim of the study was to evaluate the possibility of using chokeberry juice concentrate as a component of an osmotic solution to enrich apple samples with natural bio-ingredients and obtain dried apples with increased content of ingredients with antioxidant properties; pro-healthy apple chips. The research material consisted of apples that underwent osmotic dehydration in solutions of sucrose or sucrose and chokeberry juice concentrate and then were dried by the freeze-drying or the hybrid method. The freeze-drying was more beneficial for maintaining the vitamin C content, while the use of the hybrid method resulted in the preservation of more polyphenolic compounds. The sensory evaluation indicated the need to modify the composition of the osmoactive solution. Due to the use of chokeberry juice concentrate, the content of vitamin C, polyphenols, and the antioxidant activity of dried apples was increased.  相似文献   
326.
327.
The modern technologies use many multilayer composites comprising, the connection of different classes substrates: ceramics, metals, polymers, etc. In this work we focused our attention on an application of confocal micro-Raman spectroscopy to study the multilayer composites. Different multilayer model systems were used to check the role of the confocal mode. The problem of the transparency of layer, and their thickness were discussed. The procedure of determination of interfaces from so-called depth profiles and their first derivatives was also presented.  相似文献   
328.
The Reactions of tBu2P–P=P(Me)tBu2 and (Me3Si)tBuP–P=P(Me)tBu2 with PR3 tBu2P–P=P(Me)tBu2 ( 1 ) reacts at 20 °C with PMe3, PEt3, P(c‐Hex)3, P(p‐Tol)3, PPh2Me, PPh2Et, PPhEt2, PPh2iPr, PPh3 and P(NEt2)3 yielding tBu2P–P=PR3 and tBu2PMe; however, PtBu3, PtBu2(SiMe3) and tBu2PCl don't. tBu2PH and 1 form tBu2P–PH–PtBu2 which yields tBu2P–P=PEt3 when treated with PEt3. Ph2PH, tBuPH2, PH3, Ph2PCl and EtOH don't substitute the tBu2PMe group in 1 , instead, the molecule is decomposed. With PEt3, (Me3Si)tBuP–P=P(Me)tBu2 forms (Me3Si)tBuP–P=PEt3. The compounds tBu2P–P=PR3 decompose at 20 °C to different degrees giving P‐rich consecutive products of the phosphinophosphinidene.  相似文献   
329.
Coordination Chemistry of P‐rich Phosphanes and Silylphosphanes. XXIV. Formation and Structure of [μ‐(1,2 : 2‐η‐tBu2P–P){Mo(CO)2cp′}2] [cp′Mo(CO)2]2 (cp′ = C5H4tBu) reacts with tBu2P–P=P(Me)tBu2 to yield the compound [μ‐(1,2 : 2‐η‐tBu2P–P){Mo(CO)2cp′}2], which crystallizes in the space group P212121 with a = 1202.42(7), b = 1552.48(8), and c = 1765.3(1) pm.  相似文献   
330.
The routine techniques currently applied for the determination of nicotine and its major metabolites, cotinine, and trans-3′-hydroxycotinine, in biological fluids, include spectrophotometric, immunoassays, and chromatographic techniques. The aim of this study was to develop, and compare two new chromatographic methods high-performance liquid chromatography coupled to triple quadrupole mass spectrometry (HPLC-QQQ-MS/MS), and RP-HPLC enriched with chaotropic additives, which would allow reliable confirmation of tobacco smoke exposure in toxicological and epidemiological studies. The concentrations of analytes were determined in human plasma as the sample matrix. The methods were compared in terms of the linearity, accuracy, repeatability, detection and quantification limits (LOD and LOQ), and recovery. The obtained validation parameters met the ICH requirements for both proposed procedures. However, the limits of detection (LOD) were much better for HPLC-QQQ-MS/MS (0.07 ng mL−1 for trans-3′-hydroxcotinine; 0.02 ng mL−1 for cotinine; 0.04 ng mL−1 for nicotine) in comparison to the RP-HPLC-DAD enriched with chaotropic additives (1.47 ng mL−1 for trans-3′-hydroxcotinine; 1.59 ng mL−1 for cotinine; 1.50 ng mL−1 for nicotine). The extraction efficiency (%) was concentration-dependent and ranged between 96.66% and 99.39% for RP-HPLC-DAD and 76.8% to 96.4% for HPLC-QQQ-MS/MS. The usefulness of the elaborated analytical methods was checked on the example of the analysis of a blood sample taken from a tobacco smoker. The nicotine, cotinine, and trans-3′-hydroxycotinine contents in the smoker’s plasma quantified by the RP-HPLC-DAD method differed from the values measured by the HPLC-QQQ-MS/MS. However, the relative errors of measurements were smaller than 10% (6.80%, 6.72%, 2.04% respectively).  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号