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Background: Mental illness has always been subject to stigma and discrimination. There are a number of studies on public attitudes towards people with mental illness. Long-term studies, however, examining changes over time are scarce. Aims: The aim of this study was to examine potential changes concerning attitudes between 1976 and 2014 in Vilhelmina, a community in northern Sweden. Methods: A postal questionnaire was sent out to a random sample of 500 adults aged 18–70 years. The same questionnaire has previously been used in 1976 and 2003. Results: The attitudes towards people with mental illness have not generally become more positive over the years. In 2014 almost a quarter of the population still think that “people with mental illness commit violentX acts more than others”. Even more people in 2014 than in 1976 agree to the statement that “mental illness harms the reputation more than a physical disease” (77.2% versus 52.8%). People with low educational level have more negative views than people with higher education. Younger respondents, < 20 years, had a more positive view than the older age groups. Almost 70% of the respondents would advise someone with psychological problems to seek a psychiatrist but only 23% of the respondents would follow their own advice. Psychotherapy has been and is still highly appreciated. As regards medication the perception is more critical, but there has been a significant change, however, to a more positive attitude towards medication since 1976. Conclusion: Attitudes towards mental illness and mentally ill people have not changed substantially over time.  相似文献   
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Parkin and the glial cell line–derived neurotrophic factor (GDNF) receptor RET have both been independently linked to the dopaminergic neuron degeneration that underlies Parkinson’s disease (PD). In the present study, we demonstrate that there is genetic crosstalk between parkin and the receptor tyrosine kinase RET in two different mouse models of PD. Mice lacking both parkin and RET exhibited accelerated dopaminergic cell and axonal loss compared with parkin-deficient animals, which showed none, and RET-deficient mice, in which we found moderate degeneration. Transgenic expression of parkin protected the dopaminergic systems of aged RET-deficient mice. Downregulation of either parkin or RET in neuronal cells impaired mitochondrial function and morphology. Parkin expression restored mitochondrial function in GDNF/RET-deficient cells, while GDNF stimulation rescued mitochondrial defects in parkin-deficient cells. In both cases, improved mitochondrial function was the result of activation of the prosurvival NF-κB pathway, which was mediated by RET through the phosphoinositide-3-kinase (PI3K) pathway. Taken together, these observations indicate that parkin and the RET signaling cascade converge to control mitochondrial integrity and thereby properly maintain substantia nigra pars compacta dopaminergic neurons and their innervation in the striatum. The demonstration of crosstalk between parkin and RET highlights the interplay in the protein network that is altered in PD and suggests potential therapeutic targets and strategies to treat PD.  相似文献   
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Introduction

The frequency of aac(6′)-Ib-cr gene in ESBL-producing strains of Klebsiella pneumoniae and Escherichia coli is unknown, in Chile.

Methodology

The aac(6′)-Ib and aac(6’)-Ib-cr genes were investigated using polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), and sequencing, in strains isolated from 10 Chilean hospitals between 2008-2009.

Results

The aac(6’)-Ib-cr gene was detected in 54% of K. pneumoniae and 74% of E. coli strains. The CIM50 of CIP was higher among strains harboring aac(6’)-Ib-cr, 8 times higher in K. pneumoniae and 4 times higher in E. coli. Moreover, both aac(6’)-Ib and aac(6’)-Ib-cr were simultaneously found in 13 K. pneumoniae and 3 E. coli isolates.

Conclusion

This is the first report of aac(6’)-Ib-cr in ESBL-producing strains of K. pneumoniae and E. coli isolated from in-patients in Chilean hospitals located along an area of more than 2,800 Km.  相似文献   
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N‐[(1S)‐1‐(aminocarbonyl)‐2‐methylpropyl]‐1‐(cyclohexylmethyl)‐1H‐indazole‐3‐carboxamide (AB‐CHMINACA) is a recently introduced synthetic cannabinoid. At present, no information is available about in vitro or in vivo human metabolism of AB‐CHMINACA. Therefore, biomonitoring studies to screen AB‐CHMINACA consumption lack any information about the potential biomarkers (e.g. metabolites) to target. To bridge this gap, we investigated the in vitro metabolism of AB‐CHMINACA using human liver microsomes (HLMs). Formation of AB‐CHMINACA metabolites was monitored using liquid chromatography coupled to time‐of‐flight mass spectrometry. Twenty‐six metabolites of AB‐CHMINACA were detected including seven mono‐hydroxylated and six di‐hydroxylated metabolites and a metabolite resulting from N‐dealkylation of AB‐CHMINACA, all produced by cytochrome P450 (CYP) enzymes. Two carboxylated metabolites, likely produced by amidase enzymes, and five glucuronidated metabolites were also formed. Five mono‐hydroxylated and one carboxylated metabolite were likely the major metabolites detected. The involvement of individual CYPs in the formation of AB‐CHMINACA metabolites was tested using a panel of seven human recombinant CYPs (rCYPs). All the hydroxylated AB‐CHMINACA metabolites produced by HLMs were also produced by the rCYPs tested, among which rCYP3A4 was the most active enzyme. Most of the in vitro metabolites of AB‐CHMINACA were also present in urine obtained from an AB‐CHMINACA user, therefore showing the reliability of the results obtained using the in vitro metabolism experiments conducted to predict AB‐CHMINACA in vivo metabolism. The AB‐CHMINACA metabolites to target in biomonitoring studies using urine samples are now reliably identified and can be used for routine analysis. Copyright © 2015 John Wiley & Sons, Ltd.  相似文献   
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Statement of problem

Interim restorations are occasionally left in the mouth for extended periods and are susceptible to bacterial infiltration. Thus, dental interim cements with antibacterial properties are required.

Purpose

The purpose of this in vitro study was to determine in vitro antibacterial activity against Streptococcus mutans and to compare the diametrical tensile strength (DTSs) of dental interim cement modified with zinc oxide nanoparticles (ZnO-NPs) with that of cement modified with terpenes.

Material and methods

Antibacterial properties of ZnO-NPs, terpenes, and dental interim cement modified with ZnO-NPs and cement modified with terpenes against S mutans were tested according to minimum inhibitory concentration (MIC) and direct contact inhibition (DCI). Tensile strength levels were evaluated using DTS. Results were analyzed using the Kolmogorov-Smirnov, ANOVA, and Tamhane tests (α=.05).

Results

The MICs of ZnO-NPs and terpenes against S mutans were 61.94 μg/g and 0.25% v/v, respectively. The DCI assay under the cylinders of cement (area of contact with the agar surface) revealed significant bacterial growth inhibition on Temp-Bond NE specimens with ZnO-NPs at MIC of 495.2 μg/g (8× MIC) and with terpenes at MIC 0.999% v/v (4× MIC) (P<.05). The Temp-Bond NE cement cylinder (control group) showed the lowest DTS (1.05 ±0.27 MPa) of all other test groups. In the Zn-NPs group, the greatest increase occurred in the NP8 (8× MIC; 495.2 μg/g) group with a value of 1.50 ±0.23 MPa, a significant increase in DTS compared with the control and terpene groups (P<.05). In the terpene group, the highest increase corresponded to group T2 (2× MIC; 0.4995% v/v) with a value of 1.29 ±0.18 MPa.

Conclusions

The addition of terpenes and ZnO-NPs to interim cement showed antibacterial activity when in contact with S. mutans ATCC 25175. Both terpenes and ZnO-NPs antimicrobial agents increased diametral tensile strength.  相似文献   
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