全文获取类型
收费全文 | 1565篇 |
免费 | 91篇 |
国内免费 | 2篇 |
专业分类
耳鼻咽喉 | 21篇 |
儿科学 | 66篇 |
妇产科学 | 21篇 |
基础医学 | 128篇 |
口腔科学 | 10篇 |
临床医学 | 162篇 |
内科学 | 312篇 |
皮肤病学 | 5篇 |
神经病学 | 139篇 |
特种医学 | 126篇 |
外国民族医学 | 5篇 |
外科学 | 191篇 |
综合类 | 5篇 |
预防医学 | 165篇 |
眼科学 | 4篇 |
药学 | 55篇 |
肿瘤学 | 243篇 |
出版年
2023年 | 8篇 |
2022年 | 17篇 |
2021年 | 14篇 |
2020年 | 19篇 |
2019年 | 15篇 |
2018年 | 36篇 |
2017年 | 24篇 |
2016年 | 38篇 |
2015年 | 34篇 |
2014年 | 46篇 |
2013年 | 52篇 |
2012年 | 78篇 |
2011年 | 91篇 |
2010年 | 63篇 |
2009年 | 59篇 |
2008年 | 88篇 |
2007年 | 74篇 |
2006年 | 105篇 |
2005年 | 89篇 |
2004年 | 89篇 |
2003年 | 66篇 |
2002年 | 52篇 |
2001年 | 55篇 |
2000年 | 60篇 |
1999年 | 57篇 |
1998年 | 20篇 |
1997年 | 15篇 |
1996年 | 7篇 |
1995年 | 10篇 |
1994年 | 18篇 |
1993年 | 11篇 |
1992年 | 25篇 |
1991年 | 21篇 |
1990年 | 25篇 |
1989年 | 20篇 |
1988年 | 25篇 |
1987年 | 14篇 |
1986年 | 14篇 |
1985年 | 13篇 |
1984年 | 10篇 |
1983年 | 4篇 |
1982年 | 4篇 |
1981年 | 9篇 |
1980年 | 9篇 |
1974年 | 6篇 |
1970年 | 4篇 |
1969年 | 4篇 |
1967年 | 4篇 |
1966年 | 3篇 |
1932年 | 5篇 |
排序方式: 共有1658条查询结果,搜索用时 15 毫秒
141.
Inge S Zuhorn Dharamdajal Kalicharan George T Robillard Dick Hoekstra 《Molecular therapy》2007,15(5):946-953
For a variety of reasons, including production limitations, potential unanticipated side effects, and an immunological response upon repeated systemic administration, virus-based vectors are as yet not ideal gene delivery vehicles, justifying further research into alternatives. Unlike viral vectors, non-viral vectors pose minimal health risks, but to meet therapeutic requirements their efficacy needs major improvement. This goal may be accomplished by better defining the mechanism of non-viral gene delivery and exploiting specific cellular properties. Here we demonstrate that transfection of epithelial cells with lipoplexes is almost exclusively mediated by the beta1 integrin cell surface receptor. More important, we show that in general, adhesion receptors can be exploited by lipoplexes to gain access to cells, including difficult-to-transfect primary neural stem cells and suspension cells, thereby leading to productive transfection. We propose that adhesion receptors serve as "natural" receptors for lipoplexes. As no natural cellular receptors for lipoplexes have previously been identified, our results are an important step forward in understanding the mechanisms of non-viral gene delivery. Moreover, the finding that adhesion receptors mediate efficient non-viral gene delivery paves the way for the optimization of (standard) transfection procedures as well as ex vivo gene therapy protocols using non-viral vectors. 相似文献
142.
Rembacz KP Woudenberg J Hoekstra M Jonkers EZ van den Heuvel FA Buist-Homan M Woudenberg-Vrenken TE Rohacova J Marin ML Miranda MA Moshage H Stellaard F Faber KN 《Hepatology (Baltimore, Md.)》2010,52(6):2167-2176
Bile acid-CoA:amino acid N-acyltransferase (BAAT) conjugates bile salts to glycine or taurine, which is the final step in bile salt biosynthesis. In addition, BAAT is required for reconjugation of bile salts in the enterohepatic circulation. Recently, we showed that BAAT is a peroxisomal protein, implying shuttling of bile salts through peroxisomes for reconjugation. However, the subcellular location of BAAT remains a topic of debate. The aim of this study was to obtain direct proof for reconjugation of bile salts in peroxisomes. Primary rat hepatocytes were incubated with deuterium-labeled cholic acid (D(4)CA). Over time, media and cells were collected and the levels of D(4)CA, D(4)-tauro-CA (D(4)TCA), and D(4)-glyco-CA (D(4)GCA) were quantified by liquid chromatography-tandem mass spectrometry (LC/MS/MS). Subcellular accumulation of D(4)-labeled bile salts was analyzed by digitonin permeabilization assays and subcellular fractionation experiments. Within 24 hours, cultured rat hepatocytes efficiently (>90%) converted and secreted 100 μM D(4)CA to D(4)TCA and D(4)GCA. The relative amounts of D(4)TCA and D(4)GCA produced were dependent on the presence of glycine or taurine in the medium. Treatment of D(4)CA-exposed hepatocytes with 30-150 μg/mL digitonin led to the complete release of D(4)CA, D(4)GCA, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) (cytosolic marker). Full release of D(4)TCA, catalase, and BAAT was only observed at 500 μg/mL digitonin, indicating the presence of D(4)TCA in membrane-enclosed organelles. D(4)TCA was detected in fractions of purified peroxisomes, which did not contain D(4)CA and D(4)GCA. Conclusion: We established a novel assay to study conjugation and intra- and transcellular transport of bile salts. Using this assay, we show that cholic acid shuttles through peroxisomes for taurine-conjugation. 相似文献
143.
144.
Zuzana ikov V. Wee Yong Anita Nomden Miriam van Strien Dick Hoekstra Wia Baron 《Molecular and cellular neurosciences》2009,42(3):234-242
The extension of multiple oligodendroglial branched processes towards axons is an important event during the early stages of myelination that likely requires remodeling of the extracellular matrix (ECM) microenvironment via matrix metalloproteinases (MMPs). Here we investigated whether fibronectin-mediated inhibition of myelin sheet formation in oligodendrocytes correlated with an altered MMP activity. Our data reveal that fibronectin enhanced, in a PKC-dependent manner, the net activity of MMP-9, but not its expression, in conditioned medium of oligodendrocytes. Residual cellular MMP-9 activity on fibronectin was confined to the cell body, whereas MMP-9 activity on laminin-2 was localized along extending processes of oligodendrocytes. The mislocalization of MMP-9 activity on fibronectin correlated with a perturbed outgrowth of oligodendroglial processes. In conclusion, our findings suggest that ECM molecules influence both the net activity of secreted MMP and the spatial distribution of cell-associated MMP activity, and thereby morphological oligodendrocyte differentiation. 相似文献
145.
146.
147.
Neurofascin155 (NF155) is required for the establishment of the paranodal axo-glial junction, the predominant interaction site between myelin and axon. It has been shown that the distribution of NF155 is altered in demyelinating diseases such as multiple sclerosis (MS). However, little is known about the biochemical mechanisms underlying these changes. We therefore compared NF155 in postmortem tissue of active and chronic inactive MS lesions with white matter from healthy controls. Although NF155 showed a very similar expression in all control white matter samples, a strong individual variation was observed in MS-lesions with NF155-levels reduced in most samples. At the same time an NF155-fragment was increased in MS-lesions, suggesting that NF155 is subject to protein degradation in lesion sites. Interestingly, the association of NF155 to membrane microdomains (rafts) was reduced in all lesions, irrespective of the amount of NF155, indicating that membrane association of NF155 was generally affected. Therefore, myelin fractionation experiments were performed to analyze the fate of paranodal proteins during demyelination. Although NF155 was enriched in heavy myelin from both control white matter and active MS-lesions, association of Caspr1/paranodin with heavy myelin was abolished in MS-lesions, demonstrating that paranodal junctions are disrupted. In conclusion, the data support the hypothesis that efficient raft-association of NF155 is essential for the assembly of the paranodal junction and demonstrate that reduced association of NF155 to lipid rafts is accompanied by the disassembly of the paranodal junction and thus contributes to the demyelination process in MS. 相似文献
148.
149.
150.