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41.
An algorithm to detect unexpected increases in frequency of reports of adverse events in EudraVigilance
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Luis C. Pinheiro Gianmario Candore Cosimo Zaccaria Jim Slattery Peter Arlett 《Pharmacoepidemiology and drug safety》2018,27(1):38-45
Purpose
The European Medicines Agency developed an algorithm to detect unexpected increases in frequency of reports, to enhance the ability to detect adverse events that manifest as increases in frequency, in particular quality defects, medication errors, and cases of abuse or misuse.Methods
An algorithm based on a negative binomial time‐series regression model run on 6 sequential observations prior to the monitored period was developed to forecast monthly counts of reports. A heuristic model to capture increases in counts when the previous 4 observations were null supplemented the regression. Count data were determined at drug‐event combination. Sensitivity analyses were run to determine the effect of different methods of pooling or stratifying count data. Positive retrospective detections and positive predictive values (PPVs) were determined.Results
The algorithm detected 8 of the 13 historical concerns, including all concerns of quality defects. The highest PPV (1.29%) resulted from increasing the lower count threshold from 3 to 5 and including literature reports in the counts. Both the regression model and the heuristic model components to the algorithm contributed to the detection of concerns. Sensitivity analysis indicates that stratification by commercial product reduces the PPV but suggests that pooling counts of related events may improve it.Conclusion
The results are encouraging and suggest that the algorithm could be useful for the detection of concerns that manifest as changes in frequency of reporting; however, further testing, including in prospective use, is warranted. 相似文献42.
Danilo Di Bona Janardan P. Pandey Anna Aiello Massimo Bilancia Giuseppina Candore Calogero Caruso Claudia Colomba Giovanni Duro Mattia Emanuela Ligotti Luigi Macchia Sergio Rizzo Giulia Accardi 《Immunology》2020,159(2):178-182
Hepatitis B virus (HBV) infection causes a self-limiting disease in most individuals. However, < 10% of infected subjects develop a chronic disease. Genetic host variability of polymorphic genes at the interface of innate and acquired immunity, such as killer immunoglobulin-like receptors (KIR), their human leucocyte antigen (HLA) and IgG allotypes (GM), could explain this different clinical picture. We previously showed a protective role of the KIR2DL3 gene for the development of chronic hepatitis B (CHB), and a detrimental role of the KIR ligand groups, HLA-A-Bw4 and HLA-C2. We have expanded the previous analysis genotyping patients for GM23 and GM3/17 allotypes. The comparison of the patients with CHB with those who resolved HBV infection showed that the presence of GM17 allele virtually eliminated the risk of developing CHB (OR, 0·03; 95% CI, 0·004–0·16; P < 0·0001). In addition, the combination of GM17, KIR2DL3, HLA-A-Bw4 and HLA-C2 was highly sensitive to predict the outcome of HBV infection. 相似文献
43.
Carmela R. Balistreri Calogera Pisano Adriana Martorana Oreste F. Triolo Domenico Lio Giuseppina Candore Giovanni Ruvolo 《Age (Dordrecht, Netherlands)》2014,36(5)
A large variability in occurrence, complications, and age/gender manifestations characterizes individual susceptibility of sporadic thoracic aortic aneurysms (TAA), even in subjects with the same risk factor profiles. The reasons are poorly understood. On the other hand, TAA pathophysiology mechanisms remain unclear than those involved in abdominal aorta aneurysms. However, recent evidence is suggesting a crucial role of biological ageing in inter-individual risk variation of cardiovascular diseases, including sporadic TAA. Biological age rather than chronological age is a better predictor of vascular risk. Relevant assumptions support this concept. In confirming this evidence and our preliminary data, the mean of blood leukocyte telomere length, through use of terminal restriction fragment assay and in blood samples from sporadic TAA patients and controls, was examined. Telomerase activity was also analyzed in two groups. In addition, we verified the weight of genetic inflammatory variants and the major TAA risk factors in telomere/telomerase impairment. Aorta histopathological abnormalities and systemic inflammatory mediators were ultimately correlated with telomere/telomerase impairment. Data obtained demonstrated shorter telomeres and a reduced telomerase activity in TAA patients significantly associated with a genetic inflammatory risk profile, age, gender, smoking, hypertension, a histopathological phenotype, and higher levels of systemic inflammatory mediators than controls. In conclusion, telomere and telomerase activity’s detection might be used as predictor biomarkers of sporadic TAA. Their impairment also suggests a strong role of vascular ageing in sporadic TAA, evocated by both environmental and genetic inflammatory factors. 相似文献
44.
M A Modica G di Lorenzo A Galluzzo C Giordano M R Portelli G Candore C Caruso 《Autoimmunity》1990,7(2-3):87-96
Several studies have shown that HLA-B8,DR3 positive subjects may display T cell dysfunctions. Recently, a soluble form of the receptor for IL-2 (sIL-2R) has been demonstrated in human sera and in vitro-stimulated culture supernatant from human T lymphocytes. In the present paper we report sIL-2R serum levels and sIL-2R production from peripheral blood mononuclear cells in HLA-B8,DR3 positive subjects. We found that HLA-B8,DR3 positive subjects have the highest values of serum sIL-2R, but comparing the values of these subjects with those of negative ones no significant difference was observed. As regards the in vitro production of sIL-2R, no difference exists for unstimulated cultures, whereas after stimulation, the HLA-B8,DR3 positive subjects showed the lowest values compared with negative ones. It is noteworthy that these changes are observed in autoimmune diseases linked to this HLA phenotype. 相似文献
45.
Magrone T Candore G Caruso C Jirillo E Covelli V 《Current pharmaceutical design》2008,14(26):2733-2748
Many studies have been conducted on the effects of red wine polyphenols on certain diseases, primarily, coronary heart disease (CHD) and, in this respect, evidence has been demonstrated that intake of red wine is associated with a reduction of CHD symptomatology. In this framework, the purpose of this review is to illustrate the effects of polyphenols on immune cells from human healthy peripheral blood. Data will show that polyphenols are able to stimulate both innate and adaptive immune responses. In particular, the release of cytokines such as interleukin (IL)-12, interferon (IFN)-gamma, and IL-10 as well as immunoglobulins may be important for host protection in different immune related disorders. Another important aspect pointed out in this review is the release of nitric oxide (NO) from peripheral blood mononuclear cells (PBMC), stimulated by red wine polyphenols despite the fact that the majority of studies have reported NO production only by endothelial cells. Release of NO from PBMC may play an important role in cardiovascular disease, because it is known that this molecule acts as an inhibitor of platelet aggregation. On the other hand, NO exerts a protective role against infectious organisms. Finally, some molecular cytoplasmatic pathways elicited by polyphenols able to regulate certain immune responses will also be discussed. In particular, it seems that p38, a molecule belonging to the MAPK family, is involved in the release of IFN-gamma and, therefore, in NO production. All these data confirm the beneficial effects of polyphenols in some chronic diseases. 相似文献
46.
A lasting dream of human beings is to reverse or at least postpone ageing. During the last years, an increasing number of scientific meetings, articles, and books have been devoted to anti-ageing therapies. This subject, full of misleading, simplistic, or wrong ideas, is very popular among the general public, whose imagery has been fascinated by all possible tools to delay ageing, getting immortality. Here, we discuss anti-ageing strategies aimed not to rejuvenate but to slow ageing and delay the onset of age-related diseases. These approaches should be able to substantially slow down the ageing process, extending our productive, youthful lives. 相似文献
47.
Buffa S Bulati M Pellicanò M Dunn-Walters DK Wu YC Candore G Vitello S Caruso C Colonna-Romano G 《Biogerontology》2011,12(5):473-483
Elderly people show a reduced protection against new infections and a decreased response to vaccines as a consequence of impairment of both cellular and humoral immunity. In this paper we have studied memory/naïve B cells in the elderly, evaluating surface immunoglobulin expression, production of the pro- and anti-inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-10, and presence of somatic hypermutation, focusing on the IgG+IgD?CD27? double negative (DN) B cells that are expanded in the elderly. Our results show that naïve B cells from young donors need a sufficiently strong stimulus to be activated “in vitro”, while naïve B cells from old subjects are able to produce IL-10 and TNF-α when stimulated “physiologically” (α-CD40/IL-4), suggesting that these cells might play a role in the control of the immuno-inflammatory environment in the elderly. In addition, in the elderly there is an accumulation of DN B cells with a reduced rate of somatic hypermutation. Thus, DN B lymphocytes may be exhausted cells that are expanded and accumulate as a by-product of persistent stimulation or impaired germinal center formation. 相似文献
48.
Bulati M Buffa S Candore G Caruso C Dunn-Walters DK Pellicanò M Wu YC Colonna Romano G 《Ageing research reviews》2011,10(2):274-284
Immunosenescence contributes to the decreased ability of the elderly to control infectious diseases, which is also reflected in their generally poor response to new antigens and vaccination. It is known that the T cell branch of the immune system is impaired in the elderly mainly due to expansion of memory/effector cells that renders the immune system less able to respond to new antigens. B lymphocytes are also impaired in the elderly in terms of their response to new antigens. In this paper we review recent work on B cell immunosenescence focusing our attention on memory B cells and a subset of memory B cells (namely IgG(+)IgD(-)CD27(-)) that we have demonstrated is increased in healthy elderly. 相似文献
49.
Balistreri CR Caruso C Listì F Colonna-Romano G Lio D Candore G 《Mechanisms of ageing and development》2011,132(3):86-92
Toll-like receptors (TLRs) are the principal mediators of rapid microbial recognition: the lipopolysaccharide (LPS) receptor TLR4 seems to have a paradigmatic role. Single nucleotide polymorphisms (SNPs) in the TLR4 gene, such as +896A/G, known to attenuate receptor signaling, have been described. The +896A/G SNP is significantly less frequent in patients with myocardial infarction, Alzheimer's disease or prostate cancer, whereas it is overrepresented in centenarians. To clarify and confirm the biological effects of +896A/G SNP and its role in the pathophysiology of age-related diseases and longevity, we assessed the levels of IL-6, TNF-α, IL-10 and eicosanoids (LTB4 and PGE2) in LPS-stimulated whole blood samples in vitro of 50 young healthy Sicilians, screened for the presence of this SNP. To evaluate the possible influence of SNPs in PTGS2 and 5-Lo genes on eicosanoid production, the enrolled individuals were also genotyped for −765G/C PTGS2 and −1708G/A 5-Lo SNPs. Both pro-inflammatory cytokines and eicosanoids were significantly lower in carriers bearing the TLR4 mutation, whereas the anti-inflammatory IL-10 values were higher. On the basis of data reported herein, some suggestions can be drawn. First, pathogen load, by interacting with the host genotype, determines the type and intensity of inflammatory responses, according to the pro-inflammatory status and tissue injury, implicated in the pathophysiology of major age-related diseases. Second, adequate control of inflammatory response might reduce the risk of these diseases, and, reciprocally, might increase the chance of extended survival in an environment with reduced antigen (that is, pathogen) load. 相似文献
50.