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1.
Nociceptin/Orphanin FQ (N/OFQ) is a 17 amino acid peptide that was deorphanized in 1995. The generation of specific agonists, antagonists and receptor deficient mice and rats has enabled progress in elucidating the biological functions of N/OFQ. Additionally, radio-imaging technologies have been advanced for investigation of this system in animals and humans. Together with traditional neurobehavioral techniques, these tools have been utilized to identify the biological significance of the N/OFQ system and its interacting partners. The present review focuses on the role of N/OFQ in the regulation of feeding, body weight homeostasis, stress, the stress-related psychiatric disorders of depression and anxiety, and in drug and alcohol dependence. Critical evaluation of the current scientific preclinical literature suggests that small molecule modulators of nociceptin opioid peptide receptors (NOP) might be useful in the treatment of diseases related to these biological functions. In particular, the literature data suggest that antagonism of NOP receptors will produce anti-obesity and antidepressant activities in humans. However, there are also contradictory data discussed. The current literature on the role of N/OFQ in anxiety and addiction, on the other hand points primarily to a role of agonist modulation being potentially therapeutic. Some drug-like molecules that function either as agonists or antagonists of NOP receptors have been optimized for human clinical study to test some of these hypotheses. The discovery of PET ligands for NOP receptors, combined with the pharmacological tools and burgeoning preclinical data set discussed here bodes well for a rapid advancement of clinical understanding and potential therapeutic benefit.  相似文献   
2.

Purpose

To identify and compare predictors of local tumor progression (LTP)-free survival (LTPFS) after radiofrequency (RF) ablation and microwave (MW) ablation of colorectal liver metastases (CLMs).

Materials and Methods

This is a retrospective review of CLMs ablated from November 2009 to April 2015 (110 patients). Margins were measured on contrast-enhanced computed tomography (CT) 6 weeks after ablation. Clinical and technical predictors of LTPFS were assessed using a competing risk model adjusted for clustering.

Results

Technique effectiveness (complete ablation) was 93% (79/85) for RF ablation and 97% (58/60) for MW ablation (P = .47). The median follow-up period was significantly longer for RF ablation than for MW ablation (56 months vs. 29 months) (P < .001). There was no difference in the local tumor progression (LTP) rates between RF ablation and MW ablation (P = 0.84). Significant predictors of shorter LTPFS for RF ablation on univariate analysis were ablation margins 5 mm or smaller (P < .001) (hazard ratio [HR]: 14.6; 95% confidence interval [CI]: 5.2–40.9) and perivascular tumors (P = .021) (HR: 2.2; 95% CI: 1.1–4.3); both retained significance on multivariate analysis. Significant predictors of shorter LTPFS on univariate analysis for MW ablation were ablation margins 5 mm or smaller (P < .001) (subhazard ratio: 11.6; 95% CI: 3.1–42.7) and no history of prior liver resection (P < .013) (HR: 3.2; 95%: 1.3–7.8); both retained significance on multivariate analysis. There was no LTP for tumors ablated with margins over 10 mm (median LTPFS: not reached). Perivascular tumors were not predictive for MW ablation (P = .43).

Conclusions

Regardless of the thermal ablation modality used, margins larger than 5 mm are critical for local tumor control, with no LTP noted for margins over 10 mm. Unlike RF ablation, the efficiency of MW ablation was not affected for perivascular tumors.  相似文献   
3.
王芳  何湘  赵江丽  姜铮  袁静  黄留玉 《中国热带医学》2011,11(8):911-912,915
目的构建痢疾杆菌GST-IpaH4.5融合蛋白表达质粒,并在大肠杆菌(E.coli)中诱导表达。方法以痢疾杆菌福氏2a 301株全基因组为模板,PCR扩增痢疾杆菌ipaH4.5基因,在ipaH4.5的上游加上BamHⅠ酶切位点,下游加上XholⅠ酶切位点,将ipaH4.5基因定向插入质粒pGEX-4T-1中,构建原核表达质粒pGEX-IpaH4.5并转化E.coliDH5α,筛选阳性重组子,限制性内切酶切鉴定和DNA序列测定,DNA序列正确后提取质粒转化E.coli BL21,筛选阳性转化子,异丙基硫代半乳糖苷(IPTG)诱导表达,SDS-PAGE和Western blot鉴定表达结果。结果成功构建IpaH4.5原核表达质粒pGEX-IpaH4.5并表达出大小约86 000Mr的GST-IpaH4.5融合蛋白。结论 GST-IpaH4.5融合表达载体的构建,为进一步纯化IpaH4.5蛋白和研究其在痢疾杆菌致病机制中的作用奠定了基础。  相似文献   
4.
Media conditioned by regenerating murine bone marrow cells contain a stimulator of haemopoietic stem cell proliferation. Fractionated cell populations have been examined for production of this stimulatory activity in order to characterize its cellular source. The stimulator is produced by adherent, phagocytic radioresistant, Thy 1.2?, Fc+ cells in a population concentrated in a density range of 1.064 – 1.072 g/ml. The results indicate that the producer cells reside in the heterogenous mononuclear phagocytic population of the bone marrow.  相似文献   
5.
Electrical activity in the dorsal hippocampus was recorded in freely moving cats in response to intravenous administration of 5-HT1A agonist and antagonist drugs. Administration of low doses of the selective 5-HT1A agonists 8-OH-DPAT (5–20 μg/kg) and ipsapirone (20–100 μg/kg) produced rhythmic slow activity (theta) in the hippocampal EEG within 30 s. Similar effects were observed with BMY 7378 (20 and 100 μg/kg), which acts as an agonist at presynaptic (somatodendritic) 5-HT1A receptors and as an antagonist at postsynaptic 5-HT1A receptors. Power spectral analyses showed that all three compounds produced a dose-dependent increase in the EEG power occurring in the theta frequency band (3.5–8.0 Hz) as a proportion of total power from 0.25 to 30.0 Hz (relative theta power). The increase in relative theta power produced by 8-OH-DPAT (20 μg/kg) was greatly attenuated by spiperone (1 mg/kg), a highly effective 5-HT1A autoreceptor antagonist. Administration of spiperone alone had no significant effect on relative theta power. These results are discussed in relationship to the effects of these drugs on serotonergic neuronal activity. Our results suggest that preferential activation of presynaptic 5-HT1A receptors, and subsequent inhibition of serotonin neurotransmission, facilitates the appearance of hippocampal theta activity in awake cats.  相似文献   
6.
We present a label-free in vitro method for testing the toxic potentials of chemical substances using primary neuronal cells. The cells were prepared from 16-day-old NMRI mouse embryos and cultured on silicon chips (www.bionas.de) under the influence of different parathion concentrations with sensors for respiration (Clark-type oxygen electrodes), acidification (pH-ISFETs) and cell adhesion (interdigitated electrode structures, IDES). After 12 days in vitro, the sensor readouts were simultaneously recorded for 350 min in the presence of parathion applying a serial 1:3 dilution. The parathion-dependent data was fitted by logistic functions. IC50 values of approximately 105 μM, 65 μM, and 54 μM were found for respiration, acidification, and adhesion, respectively. An IC50 value of approximately 36 μM was determined from the intracellular ATP-levels of cells, which were detected by an ATP-luminescence assay using micro-well plates. While the intracellular ATP level and cell adhesion showed no deviation from a simple logistic decay, increases of approximately 29% in the respiration and 15% in the acidification rates above the control values were found at low parathion concentrations, indicating hormesis. These increases could be fitted by a modified logistic function. We believe that the label-free, continuous, multi-parametric monitoring of cell-metabolic processes may have applications in systems-biology and biomedical research, as well as in environmental monitoring. The parallel characterization of IC50 values and hormetic effects may provide new insights into the metabolic mechanisms of toxic challenges to the cell.  相似文献   
7.
Comparative studies on the irritation potential of 18 surfactants were performed using the same stock solution of surfactant for each study. The ocular irritation potential of surfactants was studied using the red blood cell test (RBC), the hen's egg test-chorioallantoic membrane (HET-CAM) and the Skinethic ocular tissue model. The skin irritation potential was assessed based on data obtained from human studies using a 24h epicutaneous patch test (ECT) and a soap chamber test (SCT). The same pH and active substance (AS) content for all surfactants tested was used depending on the test conducted. In general, clusters of substances with varying irritation potential were identified similarly by most tests. These results show that when using standardized test conditions in which pH and % AS are the same for each surfactant tested, there is a good correlation between the in vitro ocular irritation assays themselves as well as between the dermal and ocular irritation assays. In particular the RBC test seems to be not only highly predictive for ocular irritation (H(50)/DI) but also for dermal irritation and changes in barrier function (DI) induced by surfactants.  相似文献   
8.
9.
The heritable genetic variation that explains phenotypic differences in a population fluctuates for different autoimmune disorders. Particularly in multiple sclerosis (MS) etiology, modest genetic and major environmental effects emerge.Increasingly recognized as a major environmentally shaped contributor to disease and treatment outcomes are gut microbiota.As discussed here, the observed impact of gut microbiome on MS pathophysiology, involves both quantitative and functional changes in composition, metabolism, gut permeability, homeostasis and modulation of the immune system. Although the first supplementary therapeutic interventions have been approached in general autoimmune disorders they are relatively cruder and a translation of knowledge from other pathologies is valuable but still required.Consequently initial therapeutic interventions with microbiota for autoimmune disorders could be correspondingly improved.  相似文献   
10.

Objectives

To compare the accuracy of prenatal ultrasonography (US) to magnetic resonance imaging (MRI) in the characterisation of congenital lung anomalies, and to assess their agreement with final diagnosis. To evaluate the influence of additional MRI information on therapeutic management.

Methods

26 prenatal congenital lung anomalies detected consecutively between 2006 and 2012 were retrospectively evaluated. Lesions were initially observed at prenatal US and further investigated with MRI. Prenatal US and MRI imaging findings, and suggested diagnosis were compared with the final diagnosis, obtained from autopsies (4), pathological evaluation following surgical resection (15) and postnatal imaging studies (7).

Results

Postnatal diagnoses included 7 congenital pulmonary airway malformations, 8 complex lesions, 7 overinflations, 1 sequestration, 1 bronchogenic cyst, 1 blastoma and 1 bilateral lymphangioma. Suggested prenatal US and MRI diagnosis was correct in 34.6% and 46.2% of patients, respectively, mainly isolated lung lesions with typical imaging findings. Nonspecific imaging findings at US and MRI studies were observed in 38.4% of cases. In 42% of the operated anomalies, pathological dissection revealed the presence of complex anomalies. MRI changed the US diagnosis, but not the further management in 9.7% of the lesions.

Conclusions

Prenatal US and MRI showed a high accuracy in the diagnosis of isolated congenital lung lesions with typical imaging findings. However, overall characterisation rates were low, because of both a high percentage of complex lesions and of lesions with nonspecific imaging findings. MRI was better than US in characterising complex lesions, but its additional information did not influence therapy decisions.  相似文献   
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