全文获取类型
收费全文 | 1903篇 |
免费 | 135篇 |
国内免费 | 7篇 |
专业分类
耳鼻咽喉 | 28篇 |
儿科学 | 74篇 |
妇产科学 | 18篇 |
基础医学 | 210篇 |
口腔科学 | 66篇 |
临床医学 | 174篇 |
内科学 | 529篇 |
皮肤病学 | 52篇 |
神经病学 | 92篇 |
特种医学 | 159篇 |
外科学 | 142篇 |
综合类 | 79篇 |
预防医学 | 118篇 |
眼科学 | 34篇 |
药学 | 129篇 |
1篇 | |
中国医学 | 1篇 |
肿瘤学 | 139篇 |
出版年
2019年 | 17篇 |
2018年 | 26篇 |
2017年 | 16篇 |
2016年 | 28篇 |
2015年 | 39篇 |
2014年 | 31篇 |
2013年 | 64篇 |
2012年 | 65篇 |
2011年 | 74篇 |
2010年 | 47篇 |
2009年 | 59篇 |
2008年 | 71篇 |
2007年 | 65篇 |
2006年 | 87篇 |
2005年 | 81篇 |
2004年 | 75篇 |
2003年 | 79篇 |
2002年 | 55篇 |
2001年 | 52篇 |
2000年 | 35篇 |
1999年 | 44篇 |
1998年 | 50篇 |
1997年 | 64篇 |
1996年 | 52篇 |
1995年 | 46篇 |
1994年 | 41篇 |
1993年 | 43篇 |
1992年 | 27篇 |
1991年 | 23篇 |
1990年 | 21篇 |
1989年 | 25篇 |
1988年 | 24篇 |
1987年 | 21篇 |
1985年 | 19篇 |
1984年 | 26篇 |
1983年 | 19篇 |
1982年 | 20篇 |
1981年 | 24篇 |
1980年 | 19篇 |
1979年 | 34篇 |
1978年 | 17篇 |
1976年 | 26篇 |
1975年 | 27篇 |
1974年 | 21篇 |
1973年 | 22篇 |
1972年 | 20篇 |
1971年 | 15篇 |
1970年 | 20篇 |
1969年 | 23篇 |
1968年 | 19篇 |
排序方式: 共有2045条查询结果,搜索用时 31 毫秒
61.
62.
The interaction of the multimeric glycoprotein von Willebrand Factor (vWF) with its platelet membrane receptor, the glycoprotein (GP) Ib-IX complex plays a key role in the initial adhesion of platelets to the vascular subendothelium at high shear blood flow. The GP Ib-IX-binding site is only expressed following activation of vWF, a process that regulates vWF-mediated platelet adhesion. Binding of vWF to the GP Ib-IX complex involves the vWF A1 internal repeat domain, which also contains distinct binding sites for sulfatides, heparin, and the non-physiological modulators of the vWF-GP Ib-IX interaction, ristocetin and botrocetin. With the ultimate aim of further defining the mechanism of vWF modulation, we have analyzed the ability of various polyanionic compounds, including aurintricarboxylic acid, Evans blue, fucoidan, and a range of sulfated and phosphorylated sugars, to inhibit specific binding of purified vWF to immobilized sulfatides and heparin, and the ristocetin- and botrocetindependent binding of vWF to the platelet GP Ib-IX complex. Firstly, it was confirmed using a solid-phase binding assay that, like sulfatides, heparin specifically bound to a purified 39/WkiloDalton fragment of vWF (Leu-480 to Gly-718) that encompasses the A1 domain. Secondly, the ability of a number of polyanionic compounds to inhibit binding of vWF to heparin, but not to immobilized sulfatides, supported previous data suggesting that heparin and sulfatides bind to distinct sites on vWF. In addition, aurintricarboxylic acid, Evans blue and fucoidan all inhibited binding of vWF to both heparin and sulfatides with similar ICso values. Thirdly, many of the compounds tested that inhibited binding of vWF to heparin also effectively inhibited both ristocetin- and botrocetin-dependent binding of vWF to the GP Ib-IX complex on platelets, whereas none of the compounds tested blocked vWF binding to sulfatides and GP Ib-IX but not heparin. The majority of compounds tested inhibited the vWF-platelet interaction to a comparable degree in the presence of ristocetin or botrocetin, suggesting a similar mechanism for inhibition irrespective of the modulator used. These combined experiments provide evidence for an electrostatic model of vWF modulation, and suggest that the heparin-binding domain of vWF may be an important regulatory site involved in the adhesion of vWF to the platelet GP Ib-IX complex. 相似文献
63.
Platelet alpha-granule and plasma membrane share two new components: CD9 and PECAM-1 总被引:1,自引:2,他引:1
CD9 (p24) and PECAM1 (CD31) antigens are well-defined components of the platelet plasma membrane. Both are integral glycoproteins (GPs) implicated in the adhesive and aggregative properties of human platelets. In the present report, we have investigated their subcellular localization using immunoelectron microscopy. The monospecificity of the two polyclonal antibodies used was confirmed by immunoblotting. On normal resting platelets, immunolabeling for CD9 and PECAM1 was found lining the plasma membrane and the luminal face of the open canalicular system. Some labeling was also consistently found on the alpha-granule limiting membrane. This was confirmed by double labeling experiments in which fibrinogen and von Willebrand factor (vWF) were used as alpha-granule markers. CD9 and PECAM-1 were found lining the membrane of the same granules that contained fibrinogen and vWF in their matrix. CD9 and PECAM-1 thus appear to have an intracellular distribution identical to GPIIb-IIIa, a major aggregation platelet receptor. To rule out a cross-reactivity of the two polyclonal antibodies with GPIIb/IIIa, we studied PECAM1 and CD9 expression on the platelets from a patient with type I Glanzmann's thrombasthenia whose platelets are devoid of GPIIb/IIIa. The same pattern of labeling was observed for both antigens as for normal platelets. Normal platelets were further observed after stimulation by agonists that either fail to induce (ADP) or induce granule secretion (thrombin). After treatment with ADP, platelets changed shape and centralized their granules; the plasma membrane immunolabeling remained unchanged; and gold particles were still found decorating the periphery of the centralized alpha- granules. After thrombin treatment, alpha-granules fused with the platelet membrane and secretion occurred. A significant increase of labeling was then observed on the platelet surface. From these results we conclude that the alpha-granule membrane contains two additional receptors in common with the plasma membrane. This suggests that alpha- granule membrane receptors may originate from a dual mechanism: direct targeting from the Golgi complex in megakaryocytes (for alpha-granule- specific receptors such as P-selectin) or by endocytosis from the plasma membrane (for proteins distributed in the two compartments). 相似文献
64.
Lars Lickfett Alexander Bitzen Aravind Arepally Khurram Nasir Christian Wolpert Kyung Mi Jeong Ulf Krause Rainer Schimpf Thorsten Lewalter Hugh Calkins Werner Jung Berndt Lüderitz 《Europace : European pacing, arrhythmias, and cardiac electrophysiology》2004,6(1):25-31
AIMS: The number of implantable cardioverter defibrillator (ICD) implantations, as well as follow-up procedures such as generator exchanges, lead revisions and lead system upgrades, is ever-increasing. Lead revisions and implantation of additional leads require venous access at the site of the previous ICD implantation. The aim of our study was therefore to evaluate the incidence of venous obstruction after chronic transvenous ICD system implantation. METHODS AND RESULTS: One hundred and five consecutive patients admitted for their first elective ICD generator replacement were included. All patients underwent bilateral contrast venography and the images were analyzed by two attending radiologists. Venous obstruction was classified as moderate stenosis (50-75% diameter reduction), severe stenosis (>75%) or total occlusion. Venous obstruction of various degrees was found in 25% of the patients. Complete occlusion was found in 9%, severe stenosis in 6% and moderate stenosis in 10% of the patients. The incidence of venous obstruction was increased in patients with a pacemaker prior to the initial ICD system implantation (67%). No difference was found in patients with a single defibrillator lead compared with patients who had an additional superior vena cava (SVC) shocking coil. However, the presence of a second shocking coil in the SVC incorporated in a single ICD lead was associated with an increased incidence of venous obstruction. No difference was found between silicone and polyurethane insulated leads. CONCLUSION: This study shows that venous obstruction occurs relatively frequently after ICD implantation. Therefore, contrast venography should always be obtained if malfunction of a preexistent lead is suspected or a system upgrade is considered. 相似文献
65.
66.
Davidson KC Adams AM Goodson JM McDonald CE Potter JC Berndt JD Biechele TL Taylor RJ Moon RT 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(12):4485-4490
Signal transduction pathways play diverse, context-dependent roles in vertebrate development. In studies of human embryonic stem cells (hESCs), conflicting reports claim Wnt/β-catenin signaling promotes either self-renewal or differentiation. We use a sensitive reporter to establish that Wnt/β-catenin signaling is not active during hESC self-renewal. Inhibiting this pathway over multiple passages has no detrimental effect on hESC maintenance, whereas activating signaling results in loss of self-renewal and induction of mesoderm lineage genes. Following exposure to pathway agonists, hESCs exhibit a delay in activation of β-catenin signaling, which led us to postulate that Wnt/β-catenin signaling is actively repressed during self-renewal. In support of this hypothesis, we demonstrate that OCT4 represses β-catenin signaling during self-renewal and that targeted knockdown of OCT4 activates β-catenin signaling in hESCs. Using a fluorescent reporter of β-catenin signaling in live hESCs, we observe that the reporter is activated in a very heterogeneous manner in response to stimulation with Wnt ligand. Sorting cells on the basis of their fluorescence reveals that hESCs with elevated β-catenin signaling express higher levels of differentiation markers. Together these data support a dominant role for Wnt/β-catenin signaling in the differentiation rather than self-renewal of hESCs. 相似文献
67.
68.
69.
70.