全文获取类型
收费全文 | 321篇 |
免费 | 18篇 |
出版年
2023年 | 4篇 |
2022年 | 7篇 |
2021年 | 12篇 |
2020年 | 7篇 |
2019年 | 1篇 |
2018年 | 4篇 |
2017年 | 4篇 |
2016年 | 8篇 |
2015年 | 22篇 |
2014年 | 18篇 |
2013年 | 17篇 |
2012年 | 33篇 |
2011年 | 24篇 |
2010年 | 23篇 |
2009年 | 17篇 |
2008年 | 14篇 |
2007年 | 22篇 |
2006年 | 13篇 |
2005年 | 14篇 |
2004年 | 15篇 |
2003年 | 9篇 |
2002年 | 11篇 |
2001年 | 2篇 |
2000年 | 3篇 |
1999年 | 5篇 |
1997年 | 1篇 |
1996年 | 3篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1988年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 5篇 |
1983年 | 1篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1976年 | 1篇 |
1969年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有339条查询结果,搜索用时 15 毫秒
41.
The reaction of 3beta-chloro-5alpha-cholestan-6-one semicarbazone 1 with hydrogen peroxide at 0 degrees C gives 3beta-chloro-5alpha-cholestan-6-spiro-1',2',4'-triazolidine-3'-one 2 as a product. The structural assignment of the product was confirmed on the basis of its elemental, analytical and spectral data. The ab initio calculations were performed by using density functional theory (DFT) at B3LYP/6-31G* basis set in order to describe a free radical reaction mechanism. The reaction proceeds through two radical intermediates formation. The mechanism of the reaction was explained by using frontier molecular orbital (FMO), spin electronic density map, encoded electrostatic potential map and atomic charges. It was found that the localization of frontier orbitals and the flow of atomic charges of all the calculated structures support the present reaction mechanism. The molecular properties like total energy, dipole moment and hardness of each optimized structure, were also explained. Stability of all the optimized structures in this study was supported by their respective fundamental frequencies and energy minima. 相似文献
42.
Cynthia Q. Sun Ulrike Hubl Petra Hoefakker Madhusudan K. Vasudevamurthy Keryn D. Johnson 《PloS one》2014,9(4)
A new assay for the determination of lactosylceramide-2,3-sialyltransferase (SAT I, EC 2.4.99.9) and monosialoganglioside sialyltransferase (SAT IV, EC 2.4.99.2) is described. The assay utilised the commercially available fluorophore labelled sphingolipids, boron dipyrromethene difluoride (BODIPY) lactosylceramide (LacCer), and BODIPY-monosialotetrahexosylganglioside (GM1) as the acceptor substrates, for SAT I and SAT IV, respectively. HPLC coupled with fluorescence detection was used to analyse product formation. The analysis was performed in a quick and automated fashion. The assay showed good linearity for both BODIPY sphingolipids with a quantitative detection limit of 0.05 pmol. The high sensitivity enabled the detection of SAT I and SAT IV activities as low as 0.001 μU, at least 200 fold lower than that of most radiometric assays. This new assay was applied to the screening of SAT I and SAT IV activities in ovine and bovine organs (liver, heart, kidney, and spleen). The results provided evidence that young animals, such as calves, start to produce ganglioside sialyltransferases as early as 7 days after parturition and that levels change during maturation. Among the organs tested from a bovine source, spleen had the highest specific ganglioside sialyltransferase activity. Due to the organ size, the greatest total ganglioside sialyltransferase activities (SAT I and SAT IV) were detected in the liver of both bovine and ovine origin. 相似文献
43.
David A. Sandham Claire Adcock Kamlesh Bala Lucy Barker Zarin Brown Gerald Dubois David Budd Brian Cox Robin A. Fairhurst Markus Furegati Catherine Leblanc Jodie Manini Rachael Profit John Reilly Rowan Stringer Alfred Schmidt Katharine L. Turner Simon J. Watson Jennifer Willis Gareth Williams Caroline Wilson 《Bioorganic & medicinal chemistry letters》2009,19(16):4794-4798
High throughput screening identified a 7-azaindole-3-acetic acid scaffold as a novel CRTh2 receptor antagonist chemotype, which could be optimised to furnish a highly selective compound with good functional potency for inhibition of human eosinophil shape change in whole blood and oral bioavailability in the rat. 相似文献
44.
Ramesh Gannu Chinna Reddy Palem Shravan Kumar Yamsani Vamshi Vishnu Yamsani Madhusudan Rao Yamsani 《AAPS PharmSciTech》2010,11(2):976-985
The purpose of the present study was to develop and optimize reservoir-based transdermal therapeutic system (TTS) for buspirone
(BUSP), a low bioavailable drug. A three-factor, three-level Box–Behnken design was employed to optimize the TTS. Hydroxypropyl
methylcellulose, d-limonene and propylene glycol were varied as independent variables; cumulative amount permeated across rat abdominal skin
in 24 h, flux and lag time were selected as dependent variables. Mathematical equations and response surface plots were used
to relate the dependent and independent variables. The statistical validity of polynomials was established, and optimized
formulation factors were selected by feasibility and grid search. Validation of the optimization study with seven confirmatory
runs indicated high degree of prognostic ability of response surface methodology. BUSP-OPT (optimized formulation) showed
a flux 104.6 μg cm−2 h−1, which could meet target flux. The bioavailability studies in rabbits showed that about 2.65 times improvement (p < 0.05) in bioavailability, after transdermal administration of BUSP-OPT compared to oral solution. The ex vivo–in vivo correlation was found to have biphasic pattern and followed type A correlation. Reservoir-based TTS for BUSP was developed
and optimized using Box–Behnken statistical design and could provide an effective treatment in the management of anxiety. 相似文献
45.
46.
In addition to the threats of habitat loss and degradation, adult males of the Asian elephant Elephas maximus also face greater threats from ivory poaching and conflict with humans. To understand the impact of these threats, conservationists need robust estimates of abundance and vital rates specifically for the adult male segment of elephant populations. By integrating the identification of individual male elephants in a population from distinct morphology and natural markings, with modern capture–recapture (CR) sampling designs, it is possible to estimate various demographic parameters that are otherwise difficult to obtain from this long-lived and wide-ranging megaherbivore. In this study, we developed systematic individual identification protocols and integrated them into CR sampling designs to obtain capture histories and thereby estimate the abundance of adult bull elephants in a globally important population in southern India. We validated these estimates against those obtained from an independent method combining line-transect density estimates with age–sex composition data for elephants. The sampled population was open to gains and losses between sampling occasions. The abundance of adult males in the 176 km2 study area was (SÊ ) = 134(14.20) and they comprised 14% (±1%) of the total elephant population. Time-specific abundance estimates for each sampling occasion showed a distinct increase in adult male numbers over the sampling period, explained by seasonal patterns of local migration. CR-based estimates for adult male abundance closely matched estimates from distance-based methods. Thus, while providing abundance data of comparable rigour and precision, photographic CR methods permit estimation of demographic parameters for the Asian elephant that are both urgently needed and difficult to obtain. 相似文献
47.
Shyam Sundar Sharma Md Aminul Islam Anoop Anand Malik Kamlesh Kumar Madan Singh Negi Shashi Bhushan Tripathi 《Physiology and Molecular Biology of Plants》2016,22(2):193-205
Phenotypic variation of important seed traits like seed length, seed breadth, seed thickness, 100 seed weight and seed oil content were recorded in a total of 157 collected accessions of Pongamia. Out of these, fatty acid profiles of 38 accessions selected based on their high and low oil content was analyzed. Fatty acid profile revealed high variability in stearic, oleic and linoleic acid which varied from 0.42 to 10.61 %, 34.34 to 74.58 %, and 7.00 to 31.28 % respectively. Variations in palmitic and linolenic acid were small. Iodine value, saponification number and cetane number (CN) of fatty acid methyl esters (FAME) of seed oil ranges from 186.99 to 201.25, 81.13 to 108.19 and 46.16 to 56.47 respectively. Fatty acid compositions, degree of unsaturation and CN are the important parameters, which are used to determine quality of FAME were used as biodiesel. Some of the Pongamia accessions identified were higher in oil content while some accessions showed higher degree of unsaturation and a few of them had CN values higher than 55. Genetic diversity analysis with six TE-AFLP primers generated a total of 334 bands out of which 174 (52.10 %) were polymorphic. The genetic similarity ranged from 0.11 to 0.47. These findings clearly showed high level of genetic diversity and all economically desirable traits were not present in a single genotype of Pongamia. All these traits could be selected from these CPTs and transfer to a single elite variety through selection and breeding programme and could be utilized for large scale multiplication and plantation to produce high quantity and quality biodiesel in future. 相似文献
48.
Hydrophobic interaction of 8-anilino-1-naphthalene sulfonic acid (ANS) with proteins is one of the widely used methods for characterizing/detecting partially folded states of proteins. We have carried out a systematic investigation on the effect of ANS, a charged hydrophobic fluorescent dye, on structural properties of acid-unfolded horse heart cytochrome c at pH 2.0 by a combination of optical methods and electrospray ionization mass spectroscopy (ESI MS). ANS was found to induce, a secondary structure similar to native protein and quenching of fluorescence of tryptophan residue, in the acid-unfolded protein. However, the tertiary structure was found to be disrupted thus indicating that ANS stabilizes a molten globule state in acid-unfolded protein. To understand the mechanism of ANS-induced folding of acid-unfolded cytochrome c, comparative ESI MS, soret absorption, and tryptophan fluorescence studies using nile red, a neutral hydrophobic dye, and ANS were carried out. These studies suggested that, at low pH, electrostatic interactions between negatively charged ANS molecules and positively charged amino acid residues present in acid-unfolded cytochrome c are probably responsible for ANS-induced folding of acid-unfolded protein to partially folded compact state or molten globule state. This is the first experimental demonstration of ANS induced folding of unfolded protein and puts to question the usefulness of ANS for characterization/determination of partially folded intermediates of proteins observed under low pH conditions. 相似文献
49.
Hayden MR Karuparthi PR Habibi J Lastra G Patel K Wasekar C Manrique CM Ozerdem U Stas S Sowers JR 《Experimental biology and medicine (Maywood, N.J.)》2008,233(9):1109-1123
CONTEXT: The transgenic human islet amyloid polypeptide (HIP) rat model of type 2 diabetes mellitus (T2DM) parallels the functional and structural changes in human islets with T2DM. OBJECTIVE: The transmission electron microscope (TEM) was utilized to observe the ultrastructural changes in islet microcirculation. METHODS: Pancreatic tissue from male Sprague Dawley rats (2, 4, 8, 14 months) were used as controls (SDC) and compared to the 2-, 4-, 8- and 14-month-old HIP rat models. RESULTS: The 2-month-old HIP model demonstrated no islet or microcirculation remodeling changes when compared to the SDC models. The 4-month-old HIP model demonstrated significant pericapillary amyloid deposition and diminution of pericyte foot processes as compared to the SDC models. The 8-month-old model demonstrated extensive islet amyloid deposition associated with pericyte and beta-cell apoptosis when compared with SDC. The 14-month-old HIP model demonstrated a marked reduction of beta-cells and intra-islet capillaries with near complete replacement of islets by amyloidoses. Increased cellularity in the region of the islet exocrine interface was noted in the 4- to 14-month-old HIP models as compared to SDC. In contrast to intra-islet capillary rarefaction there was noticeable angiogenesis in the islet exocrine interface. Pericytes seemed to be closely associated with collagenosis, intra-islet adipogenesis and angiogenesis in the islet exocrine interface. CONCLUSION: The above novel findings regarding the microcirculation and pericytes could assist researchers and clinicians in a better morphological understanding of T2DM and lead to new strategies for prevention and treatment of T2DM. 相似文献
50.