全文获取类型
收费全文 | 427篇 |
免费 | 15篇 |
国内免费 | 3篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 4篇 |
妇产科学 | 2篇 |
基础医学 | 37篇 |
口腔科学 | 2篇 |
临床医学 | 47篇 |
内科学 | 69篇 |
皮肤病学 | 3篇 |
神经病学 | 55篇 |
特种医学 | 27篇 |
外科学 | 89篇 |
综合类 | 2篇 |
预防医学 | 15篇 |
眼科学 | 6篇 |
药学 | 46篇 |
肿瘤学 | 40篇 |
出版年
2023年 | 5篇 |
2022年 | 4篇 |
2021年 | 6篇 |
2020年 | 4篇 |
2019年 | 14篇 |
2018年 | 13篇 |
2017年 | 7篇 |
2016年 | 8篇 |
2015年 | 13篇 |
2014年 | 12篇 |
2013年 | 18篇 |
2012年 | 49篇 |
2011年 | 43篇 |
2010年 | 17篇 |
2009年 | 20篇 |
2008年 | 12篇 |
2007年 | 28篇 |
2006年 | 19篇 |
2005年 | 16篇 |
2004年 | 18篇 |
2003年 | 15篇 |
2002年 | 12篇 |
2000年 | 2篇 |
1999年 | 4篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1995年 | 4篇 |
1994年 | 4篇 |
1992年 | 2篇 |
1990年 | 4篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 5篇 |
1986年 | 4篇 |
1985年 | 6篇 |
1984年 | 8篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1980年 | 5篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1977年 | 4篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 4篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1971年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有445条查询结果,搜索用时 15 毫秒
1.
Patric M Schiltz German G Gomez Susana B Read Nisha V Kulprathipanja Carol A Kruse 《Journal of interferon & cytokine research》2002,22(12):1209-1216
To enhance the efficacy of cellular immunotherapy for gliomas, we tested the concept of using proinflammatory cytokine treatment with interferon-gamma (IFN-gamma) or interleukin-1beta (IL-1beta) or both to render glioma cells more susceptible to cytolysis by alloreactive cytotoxic T lymphocytes (aCTL). The cytokines, separately or in combination, were able to upregulate major histocompatibility complex (MHC) class I antigen or intercellular adhesion molecule-1 (ICAM-1) on Fischer rat 9L gliosarcoma cells. 9L cells were incubated in vitro for 24, 48, or 72 h with varying concentrations of rat IFN-gamma (0-2000 U/ml) or recombinant human IL-1 (rHUIL-1) (0-1000 U/ml) or both. By 48 h, IFN-gamma (500 U/ml) maximally induced the percentage of positive expressing cells and the relative antigen density of MHC class I and ICAM-1 on 9L cells, whereas IL-1 induced only ICAM-1 expression. Simultaneous incubation of IL-1 with IFN-gamma did not further affect the induction of class I on 9L cells more than that achieved with IFN-gamma alone. 9L cells with upregulated MHC class I and ICAM-1 expression were more sensitive to lysis by aCTL in in vitro cytotoxicity assays, regardless of whether the precursor aCTL came from naive or from 9L-immunized rats. Furthermore, inhibition of 9L cytotoxicity in assays that included blocking antibodies to MHC class I or to ICAM-1 revealed that T cell receptor (TCR) interactions with MHC class I and that ICAM-1 interactions with lymphocyte function-associated-1 (LFA-1) antigen account for a portion of the glioma lysis by aCTL. 相似文献
2.
Verhell Coleta; de Graaff Graaff Esther; Bakker Cathy E.; Willemsen Rob; Willems Patric J.; Meijer Nicolle; Galjaard Hans; Reuser Arnold J.J.; Oostra Ben A.; Hoogeveen Andre 《Human molecular genetics》1995,4(5):895-901
FMR1 protein expression was studied in different tissues. Inhuman, monkey and murine tissues, high molecular mass FMR1 proteins(6780 kDa) are found, as shown in lymphobiastoid celiiines. The identity of these proteins was confirmed by theirabsence in tissues from patients with the fragile X syndromeand a FMR1 knock-out mouse. An IIe367Asn substitution in theFMR1 protein did not aiter the transiation, processing and localizationof FMR1 proteins in lymphoblastoid cells from a patient carryingthis mutation. All the high molecular mass FMR1 proteins isolatedfrom normal lymphoblastoid cells and cells from the patientwith the IIe367Asn substitution were able to bind RNA. However,the FMR1 proteins of the patient had reduced affinity for RNAbinding at high salt concentrations. In some human, monkey andmurine tissues low molecular mass FMR1 proteins (3941kDa) were found, which had the same N terminus as the 6790kDa isoforms, but differ in their C terminus and are thereforemost likely the result of carboxy-terminal proteolytic cleavage.These low molecular mass FMR1 proteins did not bind RNA, incontrast with the high molecular mass FMR1 proteins. The significanceof these low molecular mass proteins remains to be studied. 相似文献
3.
BDNF increases release probability and the size of a rapidly recycling vesicle pool within rat hippocampal excitatory synapses 总被引:2,自引:1,他引:2
William J. Tyler Xiao-lei Zhang Kenichi Hartman Jochen Winterer Wolfgang Muller Patric K. Stanton Lucas Pozzo-Miller 《The Journal of physiology》2006,574(3):787-803
Exerting its actions pre-, post- and peri-synaptically, brain-derived neurotrophic factor (BDNF) is one of the most potent modulators of hippocampal synaptic function. Here, we examined the effects of BDNF on a rapidly recycling pool (RRP) of vesicles within excitatory synapses. First, we estimated vesicular release in hippocampal cultures by performing FM4-64 imaging in terminals impinging on enhanced green fluorescent protein (eGFP)-labelled dendritic spines – a hallmark of excitatory synapses. Consistent with a modulation of the RRP, BDNF increased the evoked destaining rate of FM4-64 only during the initial phase of field stimulation. Multiphoton microscopy in acute hippocampal slices confirmed these observations by selectively imaging the RRP, which was loaded with FM1-43 by hyperosmotic shock. Slices exposed to BDNF showed an increase in the evoked and spontaneous rates of FM1-43 destaining from terminals in CA1 stratum radiatum, mostly representing excitatory terminals of Schaffer collaterals. Variance-mean analysis of evoked EPSCs in CA1 pyramidal neurons further confirmed that release probability is increased in BDNF-treated slices, without changes in the number of independent release sites or average postsynaptic quantal amplitude. Because BDNF was absent during dye loading, imaging, destaining and whole-cell recordings, these results demonstrate that BDNF induces a long-lasting enhancement in the probability of transmitter release at hippocampal excitatory synapses by modulating the RRP. Since the endogenous BDNF scavenger TrkB-IgG prevented the enhancement of FM1-43 destaining rate caused by induction of long-term potentiation in acute hippocampal slices, the modulation of a rapidly recycling vesicle pool may underlie the role of BDNF in hippocampal long-term synaptic plasticity. 相似文献
4.
John J. Gullo Charles L. Litterst Patrick J. Maguire Branimir I. Sikic Daniel F. Hoth Paul V. Woolley 《Cancer chemotherapy and pharmacology》1980,5(1):21-26
Summary The pharmacokinetics of cis-dichlorodiamminoplatinum (II) (cisplatin) have been studied in seven patients, of whom four received the drug as a one hour infusion and three received it as a 20 h infusion. The patients receiving the drug over one hour exhibited biphasic clearance of total platinum with a rapid initial phase (8.7–22.5 min) and a prolonged second phase (30.5–106 h). Free (ultrafilterable) cisplatin was readily detectable in this group and was rapidly cleared (half-life about 22 min). The volume of distribution of the drug was 50.3–65.6 liters and it was 26.6–50% excreted in the urine in 48h. In the patients receiving the 20 h infusion, a more complex plasma elimination curve was seen, with the appearance of a secondary peak. Free drug was not detectable in these patients and they showed less urinary excretion (21.4–25.9% at 48 h) than the one hour group. Cisplatin was bound to several plasma proteins, including albumin, transferrin, and -globulin. The data indicate that cisplatin is retained in the body more extensively after a 20 h infusion than after a one hour infusion. 相似文献
5.
Giovanni Battistella Julien Niederhauser Eleonora Fornari Loyse Hippolyte Aline Gronchi Perrin Gaetan Lesca Francesca Forzano Patric Hagmann Francois J.G. Vingerhoets Bogdan Draganski Philippe Maeder Sébastien Jacquemont 《Neurobiology of aging》2013
Fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset movement disorder affecting FMR1 premutation carriers, is associated with cerebral and cerebellar lesions. The aim of this study was to test whether computational anatomy can detect similar patterns in asymptomatic FMR1 premutation carriers (mean age 46.7 years) with qualitatively normal -appearing grey and white matter on brain MRI. We used a multimodal imaging protocol to characterize brain anatomy by automated assessment of gray matter volume and white matter properties. Structural changes in the hippocampus and in the cerebellar motor network with decreased gray matter volume in lobule VI and white matter alterations of the corresponding afferent projections through the middle cerebellar peduncles are demonstrated. Diffuse subcortical white matter changes in both hemispheres, without corresponding gray matter alterations, are only identified through age × group interactions. We interpret the hippocampal fimbria and cerebellar changes as early alterations with a possible neurodevelopmental origin. In contrast, progression of the diffuse cerebral hemispheric white matter changes suggests a neurodegenerative process, leading to late-onset lesions, which may mark the imminent onset of FXTAS. 相似文献
6.
Rickard L. Sjöberg Björn Häggström Johanna Philipsson Jan Linder Marwan Hariz Patric Blomstedt 《Neurocase》2013,19(5):601-606
Ear advantage during a dichotic listening task tends to mirror speech lateralization. Previous studies in stroke patients have shown that lesions in the dominant hemisphere often seem to produce changes in ear advantage. In this study six Parkinson’s disease (PD) patients treated for motor symptoms with deep brain stimulation (DBS) of the left subthalamic nucleus (STN) were tested preoperatively and at approximately 6 and 18 months postoperatively with a dichotic listening task. Results show a significant decline of the right ear advantage over time. In three of the patients a right ear advantage preoperativley changed to a left ear advantage 18 months postoperatively. This suggests the possibility that additional longitudinal studies of this phenomenon could serve as a model for understanding changes in indirect measures of speech lateralization in stroke patients. 相似文献
7.
Rasmus Stenmark Persson Teresa Nordin Gun-Marie Hariz Karin Wårdell Lars Forsgren Marwan Hariz Patric Blomstedt 《Neuromodulation》2022,25(6):935-944
ObjectiveTo evaluate the effects of bilateral caudal zona incerta (cZi) deep brain stimulation (DBS) for Parkinson's disease (PD) one year after surgery and to create anatomical improvement maps based on patient-specific simulation of the electric field.Materials and MethodsWe report the one-year results of bilateral cZi-DBS in 15 patients with PD. Patients were evaluated on/off medication and stimulation using the Unified Parkinson's Disease Rating Scale (UPDRS). Main outcomes were changes in motor symptoms (UPDRS-III) and quality of life according to Parkinson's Disease Questionnaire-39 (PDQ-39). Secondary outcomes included efficacy profile according to sub-items of UPDRS-III and simulation of the electric field distribution around the DBS lead using the finite element method. Simulations from all patients were transformed to one common magnetic resonance imaging template space for the creation of improvement maps and anatomical evaluation.ResultsMedian UPDRS-III score off medication improved from 40 at baseline to 21 on stimulation at one-year follow-up (48%, p < 0.0005). PDQ-39 summary index did not change, but the subdomain activities of daily living (ADL) and stigma improved (25%, p < 0.03 and 75%, p < 0.01), whereas communication worsened (p < 0.03). For UPDRS-III sub-items, stimulation alone reduced median tremor score by 9 points, akinesia by 3, and rigidity by 2 points at one-year follow-up in comparison to baseline (90%, 25%, and 29%, respectively, p < 0.01). Visual analysis of the anatomical improvement maps based on simulated electrical fields showed no evident relation with the degree of symptom improvement and neither did statistical analysis show any significant correlation.ConclusionsBilateral cZi-DBS alleviates motor symptoms, especially tremor, and improves ADL and stigma in PD patients one year after surgery. Improvement maps may be a useful tool for visualizing the spread of the electric field. However, there was no clear-cut relation between anatomical location of the electric field and the degree of symptom relief. 相似文献
8.
9.
Bach P Peatfield NA Tipper SP 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2007,178(4):509-517
Humans use the same representations to code self-produced and observed actions. Neurophysiological evidence for this view comes from the discovery of the so-called mirror neurons in premotor cortex of the macaque monkey. These neurons respond when the monkey performs a particular action but also when it observes the same behavior in another individual. In humans, such direct links between perception and action seem to mediate action priming, where a response is facilitated when a similar action is observed. An issue that has not been fully resolved concerns the role of selective attention in these processes. Action priming appears to be an automatic process in the sense that the observed action can be irrelevant to the observer's task and nevertheless prime similar responses. However, it is not known whether attention has to be oriented to the action for these processes to be engaged. It is demonstrated here that spatial attention indeed has to be oriented to the action related body site for action priming to take place. Furthermore, if attention is oriented to the appropriate body site, there need be no visual cues to action for action priming to emerge. 相似文献
10.
Rationale and Design of LAPLACE‐2: A Phase 3, Randomized,Double‐Blind,Placebo‐ and Ezetimibe‐Controlled Trial Evaluating the Efficacy and Safety of Evolocumab in Subjects With Hypercholesterolemia on Background Statin Therapy 下载免费PDF全文
Jennifer G. Robinson MD MPH William J. Rogers MD Bettina S. Nedergaard MD PhD Jonathan Fialkow MD Joel M. Neutel MD David Ramstad MD MPH Ransi Somaratne MD MBA Jason C. Legg PhD Patric Nelson MPH MBA Rob Scott MD Scott M. Wasserman MD Robert Weiss MD 《Clinical cardiology》2014,37(4):195-203
Low‐density lipoprotein cholesterol (LDL‐C) levels are significantly associated with atherosclerotic cardiovascular disease (ASCVD) risk, and studies using interventions that lower LDL‐C levels have been shown to reduce the risk of ASCVD events and mortality. Statin treatment is the current first‐line therapy for lowering LDL‐C and reducing ASCVD risk. However, many patients are still unable to reach recommended LDL‐C goals on maximally tolerated statin therapy. Monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9, including evolocumab (previously AMG 145), dramatically lowered LDL‐C in phase 2 clinical trials when administered alone or in combination with a statin. The aim of this phase 3 study is to evaluate the efficacy of 12 weeks of subcutaneous evolocumab (vs placebo) administered every 2 weeks or every month in combination with a statin in patients with hypercholesterolemia and mixed dyslipidemia. This study will also provide comparative efficacy, safety, and tolerability data between evolocumab and ezetimibe when added to background atorvastatin therapy. 相似文献