全文获取类型
收费全文 | 1195篇 |
免费 | 53篇 |
国内免费 | 50篇 |
专业分类
耳鼻咽喉 | 8篇 |
儿科学 | 35篇 |
妇产科学 | 12篇 |
基础医学 | 154篇 |
口腔科学 | 25篇 |
临床医学 | 126篇 |
内科学 | 295篇 |
皮肤病学 | 11篇 |
神经病学 | 106篇 |
特种医学 | 174篇 |
外科学 | 76篇 |
综合类 | 17篇 |
预防医学 | 23篇 |
眼科学 | 75篇 |
药学 | 110篇 |
肿瘤学 | 51篇 |
出版年
2023年 | 4篇 |
2022年 | 5篇 |
2021年 | 20篇 |
2020年 | 17篇 |
2019年 | 13篇 |
2018年 | 24篇 |
2017年 | 13篇 |
2016年 | 15篇 |
2015年 | 19篇 |
2014年 | 40篇 |
2013年 | 33篇 |
2012年 | 53篇 |
2011年 | 52篇 |
2010年 | 32篇 |
2009年 | 56篇 |
2008年 | 41篇 |
2007年 | 58篇 |
2006年 | 39篇 |
2005年 | 26篇 |
2004年 | 26篇 |
2003年 | 31篇 |
2002年 | 24篇 |
2001年 | 29篇 |
2000年 | 20篇 |
1999年 | 30篇 |
1998年 | 56篇 |
1997年 | 47篇 |
1996年 | 40篇 |
1995年 | 33篇 |
1994年 | 25篇 |
1993年 | 36篇 |
1992年 | 25篇 |
1991年 | 24篇 |
1990年 | 14篇 |
1989年 | 37篇 |
1988年 | 28篇 |
1987年 | 29篇 |
1986年 | 18篇 |
1985年 | 22篇 |
1984年 | 18篇 |
1983年 | 18篇 |
1982年 | 15篇 |
1981年 | 16篇 |
1980年 | 19篇 |
1979年 | 8篇 |
1978年 | 10篇 |
1977年 | 7篇 |
1976年 | 9篇 |
1975年 | 4篇 |
1974年 | 6篇 |
排序方式: 共有1298条查询结果,搜索用时 15 毫秒
51.
Durante W; Schini VB; Kroll MH; Catovsky S; Scott-Burden T; White JG; Vanhoutte PM; Schafer AI 《Blood》1994,83(7):1831-1838
We have investigated the role of platelets in regulating the hemostatic and vasomotor properties of vascular smooth muscle. Experiments were performed to examine the effect of the releasate from activated platelets on the production of nitric oxide from interleukin-1 beta (IL- 1 beta)-treated cultured rat aortic smooth muscle cells. Treatment of vascular smooth muscle cells with IL-1 beta resulted in significant accumulation of nitrite in the culture media and in marked elevation of intracellular cyclic guanosine monophosphate (GMP) levels. The releasate from collagen-aggregated platelets blocked the IL-1 beta- mediated production of nitrite and the accumulation of cyclic GMP in smooth muscle cells in a platelet number-dependent manner. In functional assays, the perfusates from columns containing IL-1 beta- treated smooth muscle cells relaxed detector blood vessels without endothelium and the addition of IL-1 beta-treated smooth muscle cells to suspensions of platelets inhibited their thrombin-induced aggregation. The simultaneous treatment of smooth muscle cells with IL- 1 beta and the platelet releasate abolished both the vasorelaxing activities of the perfusates and the inhibition of platelet aggregation. Platelet releasates treated with a neutralizing antibody to platelet-derived growth factor (PDGF) failed to block IL-1 beta- induced nitric oxide production by the smooth muscle cells, as measured by both biochemical and functional assays. The platelet releasate from a patient with gray platelet syndrome likewise failed to block IL-1 beta-induced nitrite release by smooth muscle cells. These results demonstrate that platelets downregulate the production of nitric oxide by IL-1 beta-treated vascular smooth muscle cells through the release of PDGF. This effect may represent a novel mechanism by which platelets regulate vasomotor tone and thrombus formation at sites of vascular injury. 相似文献
52.
Development of large numbers of mast cells at sites of idiopathic chronic dermatitis in genetically mast cell-deficient WBB6F1-W/Wv mice 总被引:15,自引:1,他引:15
The normal skin and other tissues of adult mast cell-deficient WBB6F1- W/Wv or WCB6F1-Sl/Sld mice contain less than 1.0% the number of mast cells present in the corresponding tissues of the congenic normal (+/+) mice. As a result, genetically mast cell-deficient WBB6F1-W/Wv or WCB6F1-Sl/Sld mice are widely used for studies of mast cell differentiation and function. We found that mast cells developed at sites of idiopathic chronic dermatitis in WBB6F1-W/Wv mice and that the number of mast cells present in the skin of WBB6F1-W/Wv mice was proportional to the severity of the dermatitis (in ear skin, there were 33 +/- 4 mast cells/mm2 of dermis at sites of severe dermatitis v 9 +/- 3 at sites of mild dermatitis, 0.8 +/- 0.3 in skin without dermatitis, and 100 +/- 7 in the normal skin of congenic WBB6F1-+/+ mice; in back skin, the corresponding values were 2.0 +/- 0.6, 1.1 +/- 0.9, 0.025 +/- 0.025, and 26.2 +/- 3.2). The development of mast cells was a local, not systemic, consequence of the dermatitis. Thus, WBB6F1-W/Wv mice with severe dermatitis lacked mast cells in skin not showing signs of dermatitis and also in the peritoneal cavity, stomach, cecum, and tongue. Idiopathic chronic dermatitis was not associated with the local development of mast cells in WCB6F1-Sl/Sld mice, a mutant whose mast cell deficiency is due to a mechanism distinct from that of WBB6F1-W/Wv mice. These findings may have implications for understanding the nature of the mast cell deficiency in WBB6F1-W/Wv and WCB6F1-Sl/Sld mice and for the use of these mutants to analyze mast cell differentiation and function. 相似文献
53.
BACKGROUND:
Selecting candidates for plastic surgery residency training remains a challenge. In the United States, academic measures (United States Medical Licensing Exam Step I scores, medical school class rank and publications) are used as primary criteria for candidate selection for residency. In contrast, Canadian medical education de-emphasizes academic measures by using a pass-fail grading system. As a result, choosing residents from many qualified applicants may pose a challenge for Canadian programs without objective measures of academic success.METHODS:
A 25-question online survey was distributed to program directors of Canadian plastic surgery residency-training programs. Program directors commented on number of yearly residents and applicants; application sections (ranked in importance using a Likert scale); interview invitation and rank-order list determination; and their satisfaction with the selection process.RESULTS:
Ten Canadian plastic surgery program directors responded (90.9% response rate). The most important application components determining invitation to interview were letters of reference from a plastic surgeon (mean importance of 5.0 on the Likert scale), clinical electives in plastic surgery (mean 4.6) and electives with their program (mean 4.5). Applicants invited for interview were assessed on the quality of their responses to questions, maturity and personality. The majority of program directors agreed that a clinical elective with their program was important for consideration on their rank-order list. Program directors were neutral on their satisfaction with the selection process.CONCLUSION:
Canadian plastic surgery residency programs emphasize clinical electives with their program and letters of reference from colleagues when selecting applicants for interviews. In contrast to their American counterparts, Canadian program directors rely on clinical interactions with prospective residents in the absence of objective academic measures. 相似文献54.
Immunoglobulin G from patients with heparin-induced thrombocytopenia binds to a complex of heparin and platelet factor 4 总被引:6,自引:3,他引:6
Heparin-induced thrombocytopenia (HIT) is an important complication of heparin therapy. Although there is general agreement that platelet activation in vitro by the HIT IgG is mediated by the platelet Fc receptor, the interaction among the antibody, heparin, and platelet membrane components is uncertain and debated. In this report, we describe studies designed to address these interactions. We found, as others have noted, that a variety of other sulfated polysaccharides could substitute for heparin in the reaction. Using polysaccharides selected for both size and charge, we found that reactivity depended on two independent factors: a certain minimum degree of sulfation per saccharide unit and a certain minimum size. Hence, highly sulfated but small (< 1,000 daltons) polysaccharides were not reactive nor were large but poorly sulfated polysaccharides. The ability of HIT IgG to recognize heparin by itself was tested by Ouchterlony gel diffusion, ammonium sulfate and polyethylene glycol precipitation, and equilibrium dialysis. No technique demonstrated reactivity. However, when platelet releasate was added to heparin and HIT IgG, a 50-fold increase in binding of radio-labeled heparin to HIT IgG was observed. The releasate was then depleted of proteins capable of binding to heparin by immunoaffinity chromatography. Only platelet factor 4-immunodepleted releasate lost its reactivity with HIT IgG and heparin. Finally, to determine whether the reaction occurred on the surface of platelets or in the fluid phase, washed platelets were incubated with HIT IgG or heparin and after a wash step, heparin or HIT IgG was added, respectively. Reactivity was only noted when platelets were preincubated with heparin. Consistent with these observations was the demonstration of the presence of PF4 on platelets using flow cytometry. These studies indicate that heparin and other large, highly sulfated polysaccharides bind to PF4 to form a reactive antigen on the platelet surface. HIT IgG then binds to this complex with activation of platelets through the platelet Fc receptors. 相似文献
55.
IL‐4‐induced gene 1 maintains high Tob1 expression that contributes to TCR unresponsiveness in human T helper 17 cells
下载免费PDF全文
![点击此处可从《European journal of immunology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Alessio Mazzoni Manuela Capone Valentina Querci Maria Caterina Rossi Luca Beltrame Duccio Cavalieri Raffaele De Palma Francesco Liotta Lorenzo Cosmi Enrico Maggi Sergio Romagnani Francesco Annunziato 《European journal of immunology》2014,44(3):654-661
Human Th17 cells have a limited proliferative capacity compared to other T‐cell subsets. We have shown that human Th17 cells display impaired IL‐2 production due to IL‐4‐induced gene 1 (IL4I1) upregulation. Here, we show that in human Th17 cells, IL4I1 also maintains high levels of Tob1, a member of the Tob/BTG (B‐cell traslocation gene) antiproliferative protein family, which prevents cell‐cycle progression mediated by TCR stimulation. Indeed, Th17 cells exhibited higher levels of Tob1 than Th1 cells in both resting and TCR‐activated conditions. Accordingly, the expression of positive regulators of the cell cycle (cyclin A, B, C, and E and Cdk2), as well as of Skp2, which promotes Tob1 degradation, was lower in Th17 cells than in Th1 cells. Tob1 expression in human Th17 cells correlated with both RAR (retinoic acid receptor)‐related orphan receptor C (RORC) and IL4I1 levels. However, RORC was not directly involved in the regulation of Tob1 expression, whereas IL4I1 silencing in Th17 cells induced a substantial decrease of Tob1 expression. These data suggest that IL4I1 upregulation in human Th17 cells limits their TCR‐mediated expansion not only by blocking the molecular pathway involved in the activation of the IL‐2 promoter, but also by maintaining high levels of Tob1, which impairs entry into the cell cycle. 相似文献
56.
57.
58.
Munehisa Shimamura Ping Zhou Barbara Casolla Liping Qian Carmen Capone Hitomi Kurinami Costantino Iadecola Josef Anrather 《Journal of cerebral blood flow and metabolism》2013,33(8):1207-1214
Cyclooxygenase-2-derived prostaglandin E2 (PGE2) contributes to excitotoxic and ischemic neuronal cell death by engaging neuronal PGE2 type 1 receptors (EP1R). Our previous studies have shown that EP1R signaling resulted in disturbances of intracellular Ca2+ homeostasis and suppression of the pro-survival protein kinase AKT. The aim of this study was to investigate whether these pathophysiological mechanism have a role in the neuronal cell death after transient forebrain ischemia. Mice were subjected to ischemia/reperfusion by bilateral common carotid artery occlusion. Hippocampal cornu ammonis area 1 (CA1) neuronal cell death was determined 5 days after reperfusion. Animals treated with the EP1R antagonist SC51089 or EP1R-deficient mice (EP1−/−) showed significantly less neuronal injury as compared to vehicle-treated wild-type controls. Benefits of EP1R blockage were still evident 14 days after injury. Better neuronal survival was correlated with reduced neuronal caspase-3 activity and decreased nuclear translocation of the apoptosis-inducing factor . Neuroprotection could be reverted by intracerebroventricular administration of the phosphoinositide 3-kinase inhibitor and was not further increased by the calcineurin inhibitor FK506. These data implicate EP1R in postischemic neuronal apoptosis possibly by facilitating AKT inhibition. LY294002相似文献
59.
Enea Spada Giovanni Rezza Anna Rosa Garbuglia Flavia Lucia Lombardo Ornella Zuccaro Francesca Menniti Ippolito Elisabetta Cupellaro Stefania Capone Maria Rosaria Capobianchi Alfredo Nicosia Riccardo Cortese Antonella Folgori Alfonso Mele The Collaborative Study Group 《Journal of urban health》2018,95(1):99-110
So far, only three small outdated studies have investigated hepatitis C virus (HCV) incidence and risk factors among illicit drug users (DUs) in Italy. Thus, during 2007–2010, we conducted a prospective cohort study among DUs attending 17 Italian rehabilitation centers serving urban areas. Two hundred eighty-four HCV-uninfected DUs were prospectively followed by interview and anti-HCV antibody and RNA testing every 6 months. Incidence was calculated using the person-years method. Infection predictors were assessed by time-dependent Cox analysis. Participants were mostly male (83.4%), under opioid substitution therapy (OST) (78.9%), non-injecting DUs (67.9%), and with a mean age of 30.8. Ninety-one of 224 DUs initially under OST interrupted treatment during the follow-up. Overall HCV incidence was 5.83/100 person-years at risk (PYAR) [95% confidence intervals (CI), 3.63–9.38]. The incidence did not significantly differ according the participants’ sociodemographic characteristics or the degree of urbanization of the towns involved in the study. The incidence was higher for DUs under than for those not under OST (6.23 vs 4.50/100 PYAR; p = 0.681). Incidence was also higher for those with than for those without OST interruption (7.17 vs 5.04/100 PYAR; p = 0.55). However, all these differences were non-significant. At last follow-up visit, a significant decrease in frequency of sharing equipment for preparation/using drugs (by injection or not) was observed by analyzing either the whole cohort or DUs under OST only. Anti-HCV seroconversion resulted independently associated with sharing drug preparation/use equipment, backloading, having a HCV-positive sexual partner, or household and (marginally) intravenous injection. In this study, HCV incidence was non-negligible and OST seemed to lack effectiveness in reducing it. In Italy, implementation of combined harm reduction interventions and antiviral treatment of chronically infected DUs would be needed. 相似文献
60.
Microtubule reassembly in surface-activated platelets 总被引:2,自引:0,他引:2
It is generally accepted that a circumferential microtubule supports the discoid shape of resting platelets. The fate of the many-coiled polymer following platelet activation, however, has been a subject of considerable debate. Morphological investigations have suggested that the circumferential coils are constricted into tight rings around centrally concentrated organelles during platelet shape change. Biochemical studies employing colchicine-binding assays, on the other hand, have indicated that the bundle of microtubules dissolves almost completely within seconds after activation and reassembles in a new location one to four minutes later. The present study has accepted the latter hypothesis in order to examine the second part of the disassembly-reassembly theory proposed in biochemical studies. Platelets exposed to low temperatures sufficient to remove all microtubules were placed on glass slides and microscope grids to cause surface activation during rewarming. The combined stimuli of rewarming and surface activation might have been expected to cause more rapid assembly than warming alone or activation alone. This was not the case. Reassembly of microtubules during rewarming and simultaneous surface activation was not accelerated. In contrast to the constriction of microtubule rings observed during activation in control platelets, the diameters of coils that developed in chilled platelets one to two hours after rewarming and surface activation were twice those of control cells. 相似文献