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1.

Background

Clear cell renal cell carcinoma (ccRCC) is known to occur across the adult lifetime traversing the spectrum of age-related organismal changes. Little is known as to how the aging process may affect the course of renal cell carcinoma (RCC) and the repertoire of genes involved.

Methods

Using The Cancer Genome Atlas (n?=?436) and Cancer Genomics of the Kidney (n?=?89) datasets, we applied regression analysis to examine associations between patient age and gene expression profiles in ccRCC tumors and normal kidney tissues. Pathway enrichment analysis was performed to identify cellular process that is affected by aging in ccRCC. Moreover, connectivity mapping analysis was used to predict age-dependent response to drug treatments.

Results

Our analysis revealed different age-dependent gene expression spectra in ccRCC and normal kidney tissues. These findings were significant and independently reproducible in both datasets examined. Age up-regulated genes, showing higher expression in older patients, were significantly enriched (false discovery rate <0.05) in normal tissues for pathways associated with immune response and extracellular matrix organization, whereas age up-regulated genes in tumors were enriched for metabolism and oxidation pathways. Strikingly, age down-regulated genes in normal cells were also enriched for metabolism and oxidation, while those in tumors were enriched for extracellular matrix organization. Further in silico analysis of potential drug targets predicted preferential efficacy of Phosphoinositide 3-kinase inhibitor or immunotherapy in association with age.

Conclusion

We report on previously unrecognized associations between age and molecular underpinnings of RCC, including age-associated expression of genes implicated in RCC development or treatment.  相似文献   
2.
Intake of red and processed meat increases the risk of colorectal cancer (CRC), whereas dairy product consumption and the intake of dietary fibre are negatively associated with this risk. We investigated the effect of (i) low-protein diets with either whey or cooked meat (beef) as the protein source and (ii) high-protein diets with cooked meat (beef) either without or with the inclusion of 10% butyrylated high-amylose maize starch (HAMSB), on the urinary metabolome of rats. Urine samples from rats were analysed using untargeted LC-MS metabolomics. The level and source of the dietary protein affected the urinary excretion of numerous metabolites indicating that several metabolic pathways were changed. The inclusion of HAMSB in a high-protein diet caused significant alterations in the excretion of several metabolites. HAMSB reduced urinary excretion of potentially harmful metabolites resulting from a high level of meat consumption.  相似文献   
3.
There is no effective vaccine for the prevention and elimination of leishmaniasis. For this reason, we assessed the protective effects of DNA vaccines containing LeIF, TSA genes alone, or LeIF–TSA fusion against cutaneous leishmaniasis pEGFP‐N1 plasmid (empty vector) and phosphate buffer saline (PBS) were used as control groups. Therefore, cellular and humoral immune responses were evaluated before and after the challenge with Leishmania major. Lesion diameter was also measured 3–12 weeks after challenge. All immunized mice with plasmid DNA encoding Leishmania antigens induced the partial immunity characterized by increased IFN‐γ and IgG2a levels compared with control groups (p < 0.001). Furthermore, the immunized mice showed significant reduction in mean lesion sizes compared with mice in empty vector and PBS groups (p < 0.05). The reduction in lesion diameter was 29.3%, 34.1%, and 46.2% less in groups vaccinated with LeIF, TSA, and LeIF‐TSA, respectively, than in PBS group at 12th week post infection. IFN/IL‐4 and IgG2a/IgG1 ratios indicated that group receiving LeIF–TSA fusion had the highest IFN‐γ and IgG2a levels. In this study, DNA immunization promoted Th1 immune response characterized by higher IFN‐γ and IgG2a levels and also reduction in lesion size. These results showed that a bivalent vaccine containing two distinct antigens may induce more potent immune responses against leishmaniasis.  相似文献   
4.
Mustard gas (MG), as a chemical warfare agent was used by the Iraqi army in Iran-Iraq conflict against military men in the battlefield in 1985.The serum levels of IgG, IgA and IgM of patients exposed to MG in the battlefield were measured by single radial immunodiffusion from day 3 up to one month after exposure to MG. The serum levels of IgG in patients showed significant decrease on day 3 after exposure to MG. However, the levels of IgG in the serum samples collected from the patients during 4-18 days after exposure to MG were found to increase. The increase in serum IgG levels in the sera of patients which were collected during 19-31 days after exposure to MG was found to be highly significant, surpassing those from the controls. The levels of serum IgA in patients during one month after exposure to MG showed alterations similar to those of serum IgG, however the serum alterations of the patients IgA, comparing to those of the normal controls were not significant. The serum levels of IgM in patients did not show marked alterations during one month after exposure to MG comparing to those of the normal controls. The initial decrease in serum levels of IgG in patients is discussed in terms of a possible leakage of IgG into the skin blisters and into other severely affected parts of the body such as respiratory system, whereas the subsequent increase in serum IgG is interpreted as due to (auto) antigenic stimulation of the patients' immune systems.  相似文献   
5.
Objective To determine the geographical distribution of Leishmania species causing cutaneous leishmaniasis (CL) and to study the genetic heterogeneity of Leishmania major isolates from different endemic areas of Iran. Methods A total of 341 isolates from lesions of patients living in 11 provinces of Iran were grown in culture medium and inoculated to BALB/c mice to detect possible visceralisation. The species were identified by isoenzyme analysis using a battery of six enzymes and kinetoplast (k) DNA‐PCR technique. Genetic variation among L. major isolates was analysed by random amplified polymorphic DNA (RAPD) technique. Results Of the total 341 isolates, 283 isolates were L. major and 58 isolates were Leishmania tropica. In rural areas, the causative agent of CL was mainly L. major (95%L. major vs. 5%L. tropica), in urban areas it was L. tropica (65%L. tropica vs. 35%L. major). All isolates of L. major and 8.6% of L. tropica isolates showed visceralisation in BALB/c mice. There is considerable genetic diversity between L. major strains from different endemic areas and even between some isolates of the same endemic area. Conclusion Leishmania major is the most frequent species in the endemic areas of CL in eleven provinces of Iran, and genetic diversity is a common feature of L. major in the country.  相似文献   
6.
Pituitary - Endoscopic transsphenoidal surgery causes nasal morbidity and negatively affects health-related quality of life (HRQoL). Knowledge on actionable symptoms that could improve...  相似文献   
7.
Dysfunction of the central dopaminergic neurotransmission has been suggested to play an important role in the etiology of certain neuropsychiatric disorders such as drug abuse. It has been shown that the dopamine D2 receptor (DRD2) gene dysfunction is associated with multi-drug addiction. Addiction to opium is the most common form of drug abuse in Iran. We studied the allelic association between DRD2 Taq I A polymorphism in 100 opium-dependent Iranian patients and 130 unrelated controls. A 310 bp (base pair) region surrounding Taq I site at the DRD2 locus was amplified by polymerase chain reaction (PCR) and the PCR product was incubated with Taq I restriction enzyme. The A1 allele remained intact while the A2 allele was cut. Significant association was observed between A1 allele and addiction in the patients group (P < 0.0001). Moreover, the frequency of A1A1 genotype was significantly higher in opium users than controls (P < 0.0001). Our result indicates that DRD2 might be involved in the pathophysiology of opium addiction.  相似文献   
8.
Sarcocystis cameli was first described in one-humped camels (Camelus dromedarius), and it is the only species which have so far reported in camels. Although more than 150 species of Sarcocystis were described in various animals, only a few data on camel Sarcocystis ultrastructure were published, and this report is the first for molecular information (DNA sequence and RLFP digestion pattern). The main objective of the present work is to characterize Sarcocystis isolated from camels by electron microscopy and PCR-RFLP methods. Muscle samples were taken from the fresh esophagus, diaphragm, skeletal muscles, and heart of one-humped camels (C. dromedarius) slaughtered in abattoirs of Tehran and Ghazvin provinces, Iran. The dissection and trypsin digestion techniques were applied for the detection of the cysts. The infected samples were fixed in glutaraldehyde and/or frozen at −20°C until use for ultrastructural and molecular studies, respectively. The ultrastructural and molecular studies were carried out contemporaneously. The 18S rRNA gene of the parasites was amplified by PCR. The PCR products were cloned into a pTZ57R/T and sequenced. In addition, the PCR products were digested separately with each of the four restriction enzymes for RFLP. Our results indicated that only microcysts were observed in muscle samples. The microcysts were white, elongated, spindled, and a few spiral-shaped, with mean size 260 × 75 μm which are identical with S. cameli. The ultrastructure of microcyst wall had many non-branched finger-like protrusions irregularly folded. There was a 600-bp specific band amplified after PCR with specific primers. The molecular data for camel Sarcocystis is reported for the first time in Iran and the world.  相似文献   
9.
Hydatid cyst is a chronic zoonotic disease caused by the larval stage of the dog tapeworm, Echinococcus granulosus. To identify genotype of hydatid cysts of human and sheep jackal in Ilam Province (South West of Iran), the PCR-RFLP and DNA sequencing were used. A total of 10 human and 20 sheep protoscoleces hydatid cyst samples were collected from different hospitals and slaughterhouses. Then, the gene of cox1 of mitDNA of the parasite was amplified and PCR products were cut using AluI and HpaII restriction enzymes. Finally, a number of PCR products were bi-directionally sequenced. Based on the DNA sequencing and PCR-RFLP results, human and sheep samples indicated to pertain the genotypic similarities. Our data indicated that, the genotypes of larval stage of E. granulosus is similar in both intermediate hosts. According to the phylogenetic tree, there is at least one genotype of parasite, which belongs to E. granulosous sensu stricto (G1–G3) complex and overall isolates sequences of mtDNA indicated 100 % homology with references G1, G2, and G3 sequences in the GenBank database. G1 genotype was the dominant genotype of human and livestock.  相似文献   
10.
Long-term effects of propolis administration on serum biochemical parameters of rainbow trout (Oncorhynchus mykiss) were investigated. To determine the possible toxicity and side effects of propolis, fish were fed on diets containing 0, 0.5, 1.5, 4.5 and 9 g propolis/kg diet for 8 weeks. At the end of the experiment, various seric biochemical parameters were determined. Our results showed that all dosages induced no significant alterations in growth parameters and the seric levels of total protein, albumin, globulin, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides and activities of glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, alkaline phosphatase and lactate dehydrogenase, when compared to the control group. On the basis of our findings, propolis is a non-toxic substance for rainbow trout and its long-term administration might not have any side effects.  相似文献   
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