全文获取类型
收费全文 | 1043篇 |
免费 | 91篇 |
国内免费 | 1篇 |
专业分类
1135篇 |
出版年
2023年 | 7篇 |
2022年 | 15篇 |
2021年 | 28篇 |
2020年 | 18篇 |
2019年 | 23篇 |
2018年 | 28篇 |
2017年 | 27篇 |
2016年 | 30篇 |
2015年 | 56篇 |
2014年 | 51篇 |
2013年 | 75篇 |
2012年 | 82篇 |
2011年 | 81篇 |
2010年 | 52篇 |
2009年 | 42篇 |
2008年 | 66篇 |
2007年 | 56篇 |
2006年 | 54篇 |
2005年 | 39篇 |
2004年 | 42篇 |
2003年 | 46篇 |
2002年 | 40篇 |
2001年 | 28篇 |
2000年 | 19篇 |
1999年 | 17篇 |
1998年 | 5篇 |
1997年 | 13篇 |
1996年 | 10篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1993年 | 6篇 |
1992年 | 12篇 |
1991年 | 3篇 |
1990年 | 8篇 |
1989年 | 5篇 |
1988年 | 6篇 |
1987年 | 6篇 |
1986年 | 3篇 |
1985年 | 5篇 |
1984年 | 2篇 |
1982年 | 4篇 |
1981年 | 2篇 |
1978年 | 4篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1973年 | 1篇 |
1972年 | 2篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1957年 | 1篇 |
排序方式: 共有1135条查询结果,搜索用时 15 毫秒
151.
The progressive myoclonic epilepsy of Lafora or Lafora disease (LD) is a neurodegenerative disorder characterized by recurrent seizures and cognitive deficits. With typical onset in the late childhood or early adolescence, the patients show progressive worsening of the disease symptoms, leading to death in about 10 years. It is an autosomal recessive disorder caused by the loss-of-function mutations in the EPM2A gene, coding for a protein phosphatase (laforin) or the NHLRC1 gene coding for an E3 ubiquitin ligase (malin). LD is characterized by the presence of abnormally branched water insoluble glycogen inclusions known as Lafora bodies in the neurons and other tissues, suggesting a role for laforin and malin in glycogen metabolic pathways. Mouse models of LD, developed by targeted disruption of the Epm2a or Nhlrc1 gene, recapitulated most of the symptoms and pathological features as seen in humans, and have offered insight into the pathomechanisms. Besides the formation of Lafora bodies in the neurons in the presymptomatic stage, the animal models have also demonstrated perturbations in the proteolytic pathways, such as ubiquitin-proteasome system and autophagy, and inflammatory response. This review attempts to provide a comprehensive coverage on the genetic defects leading to the LD in humans, on the functional properties of the laforin and malin proteins, and on how defects in any one of these two proteins result in a clinically similar phenotype. We also discuss the disease pathologies as revealed by the studies on the animal models and, finally, on the progress with therapeutic attempts albeit in the animal models. 相似文献
152.
153.
154.
155.
The purpose of the present study was to develop an optimized gastric floating drug delivery system (GFDDS) containing metoprolol
tartrate (MT) as a model drug by the optimization technique. A 23 factorial design was employed in formulating the GFDDS with total polymer content-to-drug ratio (X1), polymer-to-polymer ratio (X2), and different viscosity grades of hydroxypropyl methyl cellulose (HPMC) (X3) as independent variables. Four dependent variables were considered: percentage of MT release at 8 hours, T50%, diffusion coefficient, and floating time. The main effect and interaction terms were quantitatively evaluated using a mathematical
model. The results indicate that X1 and X2 significantly affected the floating time and release properties, but the effect of different viscosity grades of HPMC (K4M
and K10M) was nonsignificant. Regression analysis and numerical optimization were performed to identify the best formulation.
Fickian release transport was confirmed as the release mechanism from the optimized formulation. The predicted values agreed
well with the experimental values, and the results demonstrate the feasibility of the model in the development of GFDDS. 相似文献
156.
T. P. Prakash R. Krishnakumar K. N. Ganesh 《Nucleosides, nucleotides & nucleic acids》2013,32(7):713-728
Abstract Synthesis and spectroscopic characterization of a dinucleotide dTprA 2 having imidazole containing side chain at C8 of adenine and aminoethylamino side chain at C5′ of nucleosugar is presented. Spectroscopic results suggest that such modifications do not drastically change the conformation of the new molecule relative to that of parent derivative. An anti glycosyl torsion would place the C8-conjugated histamine close to phosphate in right orientation for putative intramolecular interaction as in ribonuclease catalytic site. 相似文献
157.
158.
Irvine GB El-Agnaf OM Shankar GM Walsh DM 《Molecular medicine (Cambridge, Mass.)》2008,14(7-8):451-464
Developing effective treatments for neurodegenerative diseases is one of the greatest medical challenges of the 21st century. Although many of these clinical entities have been recognized for more than a hundred years, it is only during the past twenty years that the molecular events that precipitate disease have begun to be understood. Protein aggregation is a common feature of many neurodegenerative diseases, and it is assumed that the aggregation process plays a central role in pathogenesis. In this process, one molecule (monomer) of a soluble protein interacts with other monomers of the same protein to form dimers, oligomers, and polymers. Conformation changes in three-dimensional structure of the protein, especially the formation of beta-strands, often accompany the process. Eventually, as the size of the aggregates increases, they may precipitate as insoluble amyloid fibrils, in which the structure is stabilized by the beta-strands interacting within a beta-sheet. In this review, we discuss this theme as it relates to the two most common neurodegenerative conditions-Alzheimer's and Parkinson's diseases. 相似文献
159.
Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events
Guerrini M Beccati D Shriver Z Naggi A Viswanathan K Bisio A Capila I Lansing JC Guglieri S Fraser B Al-Hakim A Gunay NS Zhang Z Robinson L Buhse L Nasr M Woodcock J Langer R Venkataraman G Linhardt RJ Casu B Torri G Sasisekharan R 《Nature biotechnology》2008,26(6):669-675
Recently, certain lots of heparin have been associated with an acute, rapid onset of serious side effects indicative of an allergic-type reaction. To identify potential causes for this sudden rise in side effects, we examined lots of heparin that correlated with adverse events using orthogonal high-resolution analytical techniques. Through detailed structural analysis, the contaminant was found to contain a disaccharide repeat unit of glucuronic acid linked beta1-->3 to a beta-N-acetylgalactosamine. The disaccharide unit has an unusual sulfation pattern and is sulfated at the 2-O and 3-O positions of the glucuronic acid as well as at the 4-O and 6-O positions of the galactosamine. Given the nature of this contaminant, traditional screening tests cannot differentiate between affected and unaffected lots. Our analysis suggests effective screening methods that can be used to determine whether or not heparin lots contain the contaminant reported here. 相似文献
160.