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41.
42.
以1,4-环己二酮为原料经与哌啶缩合、还原、乙酸汞环合、碱催化分子内缩合等11步反应完成了一叶萩碱的全合成。合成品的熔点及光谱数据与天然一叶萩碱的熔点及光谱数据一致。 相似文献
43.
van Hooy-Corstjens CS Bulstra SK Knetsch ML Geusens P Kuijer R Koole LH 《Journal of biomedical materials research. Part B, Applied biomaterials》2007,80(2):339-344
Radiopacity in the vast majority of the commercially available acrylic bone cements that are used clinically is provided by particles of either BaSO(4) or ZrO(2). Literature reports have shown these agents to have a detrimental effect on some mechanical properties of the cements as well as on its biological response. We, therefore, have developed a new type of bone cement, for which radiopacity results from the presence of an iodine-containing methacrylic copolymer. The focus of the present work was the comparison of the biocompatibility of this new cement and a commercially available cement that contains barium sulfate. In vitro experiments show that both cements are cytocompatible materials, for which no toxic leachables are found. Implantation of the cements in a rabbit for three months resulted in the occasional presence of a thin fibrous tissue at the cement-bone interface, which is common for acrylic bone cements. Consideration of all the results led to the conclusion that the new cement is as biocompatible as the BaSO(4)-containing one. 相似文献
44.
Aniket D. Joshi Sandra M. Sanabria‐Bohórquez Guy Bormans Michel Koole Jan De Hoon Anne Van Hecken Marleen Depre Inge De Lepeleire Koen Van Laere Cyrille Sur Terence G. Hamill 《Synapse (New York, N.Y.)》2015,69(1):33-40
Decreased glutamatergic neurotransmission is hypothesized to be involved in the pathophysiology of schizophrenia. Inhibition of glycine transporter Type‐1 (GlyT1) reuptake is expected to increase the glutamatergic neurotransmission and may serve as treatment for cognitive and negative symptoms of schizophrenia. In this article, we present human data from a novel GlyT1 PET tracer, [18F]MK‐6577. In the process of developing a GlyT1 inhibitor therapeutic, a PET tracer can assist in determining the dose with a high probability of sufficiently testing the mechanism of action. This article reports the human PET studies with [18F]MK‐6577 for measuring GlyT1 receptor availability at baseline in normal human subjects and occupancy with a GlyT1 inhibitor, MK‐2637. Studies were also performed to measure radiation burden and the baseline test‐retest (T‐RT) variability of the tracer. The effective dose from sequential whole‐body dosimetry scans in three male subjects was estimated to be 24.5 ± 2.9 µSV/MBq (mean ± SD). The time–activity curves from T‐RT scans modeled satisfactorily using a two tissue compartmental model. The tracer uptake was highest in the pons (VT = 6.7 ± 0.9, BPND = 4.1 ± 0.43) and lowest in the cortex (VT = 2.1 ± 0.5, BPND = 0.60 ± 0.23). VT T‐RT variability measured in three subjects was <12% on average. The occupancy scans performed in a cohort of 15 subjects indicated absence of a reference region. The in vivo potency (Occ50) of MK‐2637 was determined using two methods: A: Lassen plot with a population input function (Occ50 = 106 nM, SE = 20 nM) and B: pseudo reference tissue model using cortex as the pseudo reference region (Occ50 = 141 nM, SE = 21 nM). Synapse 69:33–40, 2015. © 2014 Wiley Periodicals, Inc. 相似文献
45.
46.
Casteels C Koole M Celen S Bormans G Van Laere K 《European journal of nuclear medicine and molecular imaging》2012,39(9):1467-1477
Purpose
[18F]MK-9470 is an inverse agonist for the type 1 cannabinoid (CB1) receptor allowing its use in PET imaging. We characterized the kinetics of [18F]MK-9470 and evaluated its ability to quantify CB1 receptor availability in the rat brain.Methods
Dynamic small-animal PET scans with [18F]MK-9470 were performed in Wistar rats on a FOCUS-220 system for up to 10?h. Both plasma and perfused brain homogenates were analysed using HPLC to quantify radiometabolites. Displacement and blocking experiments were done using cold MK-9470 and another inverse agonist, SR141716A. The distribution volume (V T) of [18F]MK-9470 was used as a quantitative measure and compared to the use of brain uptake, expressed as SUV, a simplified method of quantification.Results
The percentage of intact [18F]MK-9470 in arterial plasma samples was 80?±?23?% at 10?min, 38?±?30?% at 40?min and 13?±?14?% at 210?min. A polar radiometabolite fraction was detected in plasma and brain tissue. The brain radiometabolite concentration was uniform across the whole brain. Displacement and pretreatment studies showed that 56?% of the tracer binding was specific and reversible. V T values obtained with a one-tissue compartment model plus constrained radiometabolite input had good identifiability (≤10?%). Ignoring the radiometabolite contribution using a one-tissue compartment model alone, i.e. without constrained radiometabolite input, overestimated the [18F]MK-9470 V T, but was correlated. A correlation between [18F]MK-9470 V T and SUV in the brain was also found (R 2?=?0.26–0.33; p?≤?0.03).Conclusion
While the presence of a brain-penetrating radiometabolite fraction complicates the quantification of [18F]MK-9470 in the rat brain, its tracer kinetics can be modelled using a one-tissue compartment model with and without constrained radiometabolite input. 相似文献47.
48.
Rawaha Ahmad Michel Koole Nele Evens Kim Serdons Alfons Verbruggen Guy Bormans Koen Van Laere 《Molecular imaging and biology》2013,15(4):384-390
Purpose
The type 2 cannabinoid receptor (CB2R) is part of the human endocannabinoid system and is involved in central and peripheral inflammatory processes. In vivo imaging of the CB2R would allow study of several (neuro)inflammatory disorders. In this study we have investigated the safety and tolerability of [11C]-NE40, a CB2R positron emission tomography (PET) ligand, in healthy human male subjects and determined its biodistribution and radiation dosimetry.Procedure
Six healthy male subjects (age 20–65 years) underwent a dynamic series of nine whole-body PET/CT scans for up to 140 min, after injection of an average bolus of 286 MBq of [11C]-NE40. Organ absorbed and total effective doses were calculated through OLINDA.Results
[11C]-NE40 showed high initial uptake in the spleen and a predominant hepatobiliary excretion. In the brain, rapid uptake and swift washout were seen. Organ absorbed doses were largest for the small intestine and liver, with 15.6 and 11.5 μGy/MBq, respectively. The mean effective dose was 3.64?±?0.81 μSv/MBq. There were no changes with aging observed. No adverse events were encountered.Conclusions
This first-in-man study of [11C]-NE40 showed an expected biodistribution compatible with lymphoid tissue uptake and appropriate fast brain kinetics in the healthy human brain, underscoring the potential of this tracer for further application in central and peripheral inflammation imaging. The effective dose is within the typical expected range for 11C ligands. 相似文献49.
Caroline Vandeputte Cindy Casteels Tom Struys Michel Koole Daisy van Veghel Nele Evens Anneleen Gerits Tom Dresselaers Ivo Lambrichts Uwe Himmelreich Guy Bormans Koen Van Laere 《European journal of nuclear medicine and molecular imaging》2012,39(11):1796-1806
Purpose
Recent ex vivo and pharmacological evidence suggests involvement of the endocannabinoid system in the pathophysiology of stroke, but conflicting roles for type 1 and 2 cannabinoid receptors (CB1 and CB2) have been suggested. The purpose of this study was to evaluate CB1 and CB2 receptor binding over time in vivo in a rat photothrombotic stroke model using PET.Methods
CB1 and CB2 microPET imaging was performed at regular time-points up to 2?weeks after stroke using [18F]MK-9470 and [11C]NE40. Stroke size was measured using MRI at 9.4?T. Ex vivo validation was performed via immunostaining for CB1 and CB2. Immunofluorescent double stainings were also performed with markers for astrocytes (GFAP) and macrophages/microglia (CD68).Results
[18F]MK-9470 PET showed a strong increase in CB1 binding 24?h and 72?h after stroke in the cortex surrounding the lesion, extending to the insular cortex 24?h after surgery. These alterations were consistently confirmed by CB1 immunohistochemical staining. [11C]NE40 did not show any significant differences between stroke and sham-operated animals, although staining for CB2 revealed minor immunoreactivity at 1 and 2?weeks after stroke in this model. Both CB 1 + and CB 2 + cells showed minor immunoreactivity for CD68.Conclusion
Time-dependent and regionally strongly increased CB1, but not CB2, binding are early consequences of photothrombotic stroke. Pharmacological interventions should primarily aim at CB1 signalling as the role of CB2 seems minor in the acute and subacute phases of stroke. 相似文献50.
L. Van den Bergh S. Isebaert M. Koole R. Oyen S. Joniau E. Lerut C.M. Deroose F. De Keyzer H. Van Poppel K. Haustermans 《Strahlentherapie und Onkologie》2013,189(9):789-795