全文获取类型
收费全文 | 903篇 |
免费 | 47篇 |
出版年
2023年 | 7篇 |
2022年 | 19篇 |
2021年 | 27篇 |
2020年 | 15篇 |
2019年 | 25篇 |
2018年 | 19篇 |
2017年 | 14篇 |
2016年 | 29篇 |
2015年 | 34篇 |
2014年 | 45篇 |
2013年 | 68篇 |
2012年 | 64篇 |
2011年 | 67篇 |
2010年 | 49篇 |
2009年 | 49篇 |
2008年 | 40篇 |
2007年 | 36篇 |
2006年 | 30篇 |
2005年 | 32篇 |
2004年 | 30篇 |
2003年 | 23篇 |
2002年 | 11篇 |
2001年 | 21篇 |
2000年 | 15篇 |
1999年 | 15篇 |
1998年 | 6篇 |
1997年 | 8篇 |
1995年 | 3篇 |
1994年 | 5篇 |
1993年 | 4篇 |
1992年 | 8篇 |
1991年 | 8篇 |
1990年 | 13篇 |
1989年 | 15篇 |
1988年 | 5篇 |
1987年 | 8篇 |
1986年 | 5篇 |
1985年 | 8篇 |
1984年 | 8篇 |
1983年 | 7篇 |
1981年 | 4篇 |
1979年 | 4篇 |
1977年 | 6篇 |
1976年 | 3篇 |
1975年 | 4篇 |
1974年 | 5篇 |
1973年 | 4篇 |
1972年 | 4篇 |
1971年 | 4篇 |
1970年 | 4篇 |
排序方式: 共有950条查询结果,搜索用时 31 毫秒
121.
S. R. Badu R. Melnik M. Paliy S. Prabhakar A. Sebetci B. A. Shapiro 《European biophysics journal : EBJ》2014,43(10-11):555-564
In this study, we construct novel RNA nanoclusters, RNA nanotubes made of several nanorings up to the size of 20 nm, utilizing the molecular dynamics simulation, and study their structural properties [i.e., the root mean square deviation, the radius of gyration and the radial distribution function (RDF)] in physiological solutions that can be used for drug delivery into the human body. The patterns of energy and temperature variations of the systems are also discussed. Furthermore, we study the concentration of ions around the tube as a function of time at a particular temperature. We have found that when the temperature increases, the number of ions increases within a certain distance of the tube. We report that the number of ions within this distance around the tubes decreases in quenched runs. This indicates that some ions evaporate with decrease in temperature, as has been observed in the case of the nanoring. RDF plots also demonstrate a similar trend with temperature, as was found in the case of RNA nanorings. 相似文献
122.
Effects of sex hormones on enzymic esterification of 2-(N-hydroxyacetamido)-fluorene by rat liver cytosol
下载免费PDF全文
![点击此处可从《The Biochemical journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Prabhakar D. Lotlikar 《The Biochemical journal》1970,120(2):409-416
1. Enzymic esterifications of 2-(N-hydroxyacetamido)fluorene and several other hydroxamic acids by liver cytosol were studied. Determination of 2-acetamido-3-methylthiofluorene was used for the assay. 2. With rat liver cytosol, requirement for ATP, Mg2+ and SO42− suggested formation of phosphate and sulphate esters of 2-(N-hydroxyacetamido)fluorene. 3. Rats showed sex and age differences in their activity. Liver from adult male rat was at least twice as active as liver from adult female rat. No such sex differences were found in mice, hamsters and guinea pigs. 4. Administration of testosterone (300μg/day) subcutaneously for 8 days increased the activity in the female rat by 100%, whereas diethylstilboestrol (100μg/day) had no effect. In the male rat diethylstilboestrol treatment decreased the activity by 60%, whereas testosterone pretreatment was without any effect. 5. Among various endocrine ablations such as adrenalectomy, castration, adrenalectomy–castration and hypophysectomy in the adult male rat, hypophysectomy was found to be the most effective in decreasing the activity of the liver to about 50% of control values. 6. Like 2-(N-hydroxyacetamido)fluorene, various other N-hydroxy derivatives of 2-acetamido-7-fluorofluorene, 2-acetamidophenanthrene, 4-acetamidobiphenyl and 4-acetamidostilbene were also shown to be esterified to different extents by rat liver cytosol. 相似文献
123.
124.
Optimization of parameters in the batch kinetic studies of glucose isomerisation by arthrobacter sp.
Vital parameters like temperature, pH and agitation are optimized in the kinetic studies of glucose isomerisation carried out in a batch fashion. A 4-litre fermentor with temperature, pH, agitation and other controls is used. It is found that the two parameters — temperature and pH, do not have an interacting effect on each other. A temperature of 60°C, a pH of 8.0 and a speed of 200 rpm are found to be better suited for the production of fructose syrups starting from glucose by arthrobacter sp. An upper limit of 20 minutes on the residence time is suggested for use in the design of flow reactors. 相似文献
125.
126.
Purnendu Kumar Sharma Apoorva Panda Adwait Pradhan Jiaxiang Zhang Ruchi Thakkar Chang-Hee Whang Michael A. Repka S. Narasimha Murthy 《AAPS PharmSciTech》2018,19(1):27-35
The transdermal patch formulation has many advantages, including noninvasiveness, an ability to bypass the first-pass metabolism, low dosage requirements, and prolonged drug delivery. However, the instability of solid-state drugs is one of the most critical problems observed in transdermal patch products. Therefore, a well-characterized approach for counteracting stability problems in solid-state drugs is crucial for improving the performance of transdermal patch products. This review provides insight into the solid-state stability of drugs associated with transdermal patch products and offers a comprehensive update on the various approaches being used for improving the stability of the active pharmaceutical ingredients currently being used. 相似文献
127.
Madhura Pradhan Charu Suri Sinjan Choudhary Pradeep Kumar Naik 《Journal of biomolecular structure & dynamics》2018,36(1):195-208
Beta-sitosterol (β-SITO), a phytosterol present in many edible vegetables, has been reported to possess antineoplastic properties and cancer treatment potential. We have shown previously that it binds at a unique site (the ‘SITO-site’) compared to the colchicine binding site at the interface of α- and β-tubulin. In this study, we investigated the anticancer efficacy of β-SITO against invasive breast carcinoma using MCF-7 cells. Since ‘isotypes’ of β-tubulin show tissue-specific expression and many are associated with cancer drug resistance, using computer-assisted docking and atomistic molecular dynamic simulations, we also examined its binding interactions to all known isotypes of β-tubulin in αβ-tubulin dimer. β-SITO inhibited MCF-7 cell viability by up to 50%, compared to vehicle-treated control cells. Indicating its antimetastatic potential, the phytosterol strongly inhibited cell migration. Immunofluorescence imaging of β-SITO-treated MCF-7 cells exhibited disruption of the microtubules and chromosome organization. Far-UV circular dichroism spectra indicated loss of helical stability in tubulin when bound to β-SITO. Docking and MD simulation studies, combined with MM-PBSA and MM-GBSA calculations revealed that β-SITO preferentially binds with specific β-tubulin isotypes (βII and βIII) in the αβ-tubulin dimer. Both these β-tubulin isotypes have been implicated in drug resistance against tubulin-targeted chemotherapeutics. Our data show the tubulin-targeted anticancer potential of β-SITO, and its potential clinical utility against βII and βIII isotype-overexpressing neoplasms. 相似文献
128.
1. Reaction of 2-(N-acetoxy)-acetamidofluorene with orthophosphate buffer at pH7 yielded a large quantity of water-soluble fluorene derivatives, which showed absorption peaks at 303, 290 and 280nm. Tris buffer under similar conditions gave negligible reaction. 2. Hydrolysis of polar material with acid or alkaline phosphatases liberated equimolar amounts of inorganic phosphate and an ether-extractable fluorene derivative. On the basis of its u.v. spectrum, R(F) values after paper chromatography, solubility in alkali and colour with spray reagents, the derivative was characterized tentatively as 2-acetamido-5-hydroxyfluorene. 3. Polar material also contained a reactive fluorene derivative which gave characteristic reaction products with methionine and guanosine. The reactive derivative was characterized as a phosphate ester of 2-(N-hydroxy)-acetamidofluorene. 4. It is suggested that such reactive phosphate esters may also be some of the ultimate carcinogenic metabolites of carcinogenic aromatic hydroxamic acids. 相似文献
129.
Summary The influence of different depths of submergence (6±1 and 3±1 cm) and moisture tensions (0, 20, 60, 350, 500 and 1000 millibar)
of lateritic sandy loam soil on root porosity and growth parameters of rice, variety IR8 was studied at two different growth
phases under controlled greenhouse conditions. Best rice growth occurred at 3±1 cm submergence and it significantly reduced
with the increase of soil moisture tension. Unlike other growth parameters, root length increased as the soil moisture tension
was raised. The development of pore spaces in rice roots decreased significantly with the increase in soil moisture tension.
However, higher root porosity was observed under greater depths of submergence. Irrespective of soil water condition, the
number and dry weight of the root system showed significant positive correlation with root porosity. Oxygen diffusion rate
in soil, which increased with the increasing moisture tension, was significantly and inversely related with the porosity of
rice root.
Contribution from the Agricultural Engineering Department, Indian Institute of Technology, Kharagpur, West Bengal, India. 相似文献
130.
Madhumita A. Pradhan John A. Blackford Jr. Ballachanda N. Devaiah Petria S. Thompson Carson C. Chow Dinah S. Singer S. Stoney Simons Jr. 《The Journal of biological chemistry》2016,291(1):342-354
Most of the steps in, and many of the factors contributing to, glucocorticoid receptor (GR)-regulated gene induction are currently unknown. A competition assay, based on a validated chemical kinetic model of steroid hormone action, is now used to identify two new factors (BRD4 and negative elongation factor (NELF)-E) and to define their sites and mechanisms of action. BRD4 is a kinase involved in numerous initial steps of gene induction. Consistent with its complicated biochemistry, BRD4 is shown to alter both the maximal activity (Amax) and the steroid concentration required for half-maximal induction (EC50) of GR-mediated gene expression by acting at a minimum of three different kinetically defined steps. The action at two of these steps is dependent on BRD4 concentration, whereas the third step requires the association of BRD4 with P-TEFb. BRD4 is also found to bind to NELF-E, a component of the NELF complex. Unexpectedly, NELF-E modifies GR induction in a manner that is independent of the NELF complex. Several of the kinetically defined steps of BRD4 in this study are proposed to be related to its known biochemical actions. However, novel actions of BRD4 and of NELF-E in GR-controlled gene induction have been uncovered. The model-based competition assay is also unique in being able to order, for the first time, the sites of action of the various reaction components: GR < Cdk9 < BRD4 ≤ induced gene < NELF-E. This ability to order factor actions will assist efforts to reduce the side effects of steroid treatments. 相似文献