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71.
Plaeger SF Collins BS Musib R Deeks SG Read S Embry A 《AIDS research and human retroviruses》2012,28(5):469-477
With the advent of highly effective antiretroviral therapy (ART), infection with human immunodeficiency virus (HIV) has become a chronic disease rather than a death sentence. Nevertheless, effectively treated individuals have a higher than normal risk for developing noninfectious comorbidities, including cardiovascular and renal disease. Although traditional risk factors of aging as well as treatment toxicity contribute to this risk, many investigators consider chronic HIV-associated inflammation a significant factor in such end-organ disease. Despite effective viral suppression, chronic inflammation persists at levels higher than in uninfected people, yet the stimuli for the inflammation and the mechanism by which inflammation persists and promotes disease pathology remain incompletely understood. This critical gap in scientific understanding complicates and hampers effective decision making about appropriate medical intervention. To better understand the mechanism(s) of chronic immune activation in treated HIV disease, three questions need answers: (1) what is the cause of persistent immune activation during treated HIV infection, (2) what are the best surrogate markers of chronic immune activation in this setting, and (3) what therapeutic intervention(s) could prevent or reverse this process? The NIH sponsored and convened a meeting to discuss the state of knowledge concerning these questions and the best course for developing effective therapeutic strategies. This report summarizes the findings of that NIH meeting. 相似文献
72.
Runa M. Grimholt Åshild A. Sudmann Armin P. Piehler Petter Urdal Olav Klingenberg 《Hemoglobin》2014,38(2):130-132
A new hemoglobin (Hb) variant was detected during Hb A1c measurement. DNA sequencing showed heterozygosity for the single nucleotide substitution (C?>?G) on the β-globin gene causing an amino acid change [β78(EF2)Leu→Val; HBB: c.235C?>?G]. The new Hb variant was designated Hb Ullevaal after the hospital at which it was discovered. Heterozygosity for Hb Ullevaal appears to have no clinical significance. However, it interferes with Hb A1c measurement by cation exchange high performance liquid chromatography (HPLC), causing falsely low Hb A1c concentration when using the Tosoh G7 apparatus in variant mode. 相似文献
73.
Margareta Emtner Runa Hallin Ragnheieur Harpa Arnardottir Christer Janson 《Upsala journal of medical sciences》2015,120(1):52-58
Background Weight loss and depletion of fat-free mass are common problems in patients with chronic obstructive pulmonary disease (COPD) and are related to muscular weakness and exercise intolerance. Physical training of COPD patients has good effect on exercise tolerance and quality of life. The aim of this study was to examine factors that affect change in fat-free mass after physical training, in patients with COPD.Patients Patients were examined before and after a 4-month exercise period. Weight and height were measured, and bioelectrical impedance was performed. Fat-free mass (FFM) was calculated, by a three-compartment model, and fat-free mass index (FFMI) was calculated as FFM kg/m2 and body mass index (BMI) as kg/m2. A symptom-limited ramp ergometer test and 12-minute walk test (12MWT) were performed. Dyspnoea score of daily activities was determined by Chronic Respiratory Disease Questionnaire (CRDQ). Blood was taken for analyses of C-reactive protein (CRP) and fibrinogen. Patients with a BMI <21 kg/m2 were given nutritional support during the training period.Results A total of 27 patients completed the training (64 years, FEV1 31% of predicted). Patients with low FFMI gained 1.2 kg, whereas those with normal FFMI lost 0.7 kg (p = 0.04). In multivariate analyses high age (p = 0.03), low FEV1 (p = 0.02), and a high level of dyspnoea (p = 0.01) at baseline were found to be negative predictors for increase in FFM.Conclusions Difficulties in increasing the fat-free mass in COPD patients by physical training seem to be associated with dyspnoea in daily life and impaired lung function (FEV1). 相似文献
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76.
Ling Xie Ming Zhang Qiaoqiao Liu Runa Wei Menglan Sun Qi Zhang Lingyun Hao Zhouya Xue Qihui Wang Li Yang Hongjun Wang Zhiqiang Pan 《CNS Neuroscience & Therapeutics》2023,29(10):2955-2971
Aims
Nerve injury-induced maladaptive changes in gene expression in the spinal neurons are essential for neuropathic pain genesis. Circular RNAs (ciRNA) are emerging as key regulators of gene expression. Here, we identified a nervous-system-tissues-specific ciRNA-Kat6 with conservation in humans and mice. We aimed to investigate whether and how spinal dorsal horn ciRNA-Kat6b participates in neuropathic pain.Methods
Unilateral sciatic nerve chronic constrictive injury (CCI) surgery was used to prepare the neuropathic pain model. The differentially expressed ciRNAs were obtained by RNA-Sequencing. The identification of nervous-system-tissues specificity of ciRNA-Kat6b and the measurement of ciRNA-Kat6b and microRNA-26a (miRNA-26a) expression level were carried out by quantitative RT-PCR. The ciRNA-Kat6b that targets miRNA-26a and miRNA-26a that targets Kcnk1 were predicted by bioinformatics analysis and verified by in vitro luciferase reports test and in vivo experiments including Western-blot, immunofluorescence, and RNA–RNA immunoprecipitation. The correlation between neuropathic pain and ciRNA-Kat6b, miRNA-26a, or Kcnk1 was examined by the hypersensitivity response to heat and mechanical stimulus.Results
Peripheral nerve injury downregulated ciRNA-Kat6b in the dorsal spinal horn of male mice. Rescuing this downregulation blocked nerve injury-induced increase of miRNA-26a, reversed the miRNA-26a-triggered decrease of potassium channel Kcnk1, a key neuropathic pain player, in the dorsal horn, and alleviates CCI-induced pain hypersensitivities. On the contrary, mimicking this downregulation increased the miRNA-26a level and decreased Kcnk1 in the spinal cord, resulting in neuropathic pain-like syndrome in naïve mice. Mechanistically, the downregulation of ciRNA-Kat6b reduced the accounts of miRNA-26a binding to ciRNA-Kat6b, and elevated the binding accounts of miRNA-26a to the 3′ untranslated region of Kcnk1 mRNA and degeneration of Kcnk1 mRNA, triggering in the reduction of KCNK1 protein in the dorsal horn of neuropathic pain mice.Conclusion
The ciRNA-Kat6b/miRNA-26a/Kcnk1 pathway in dorsal horn neurons regulates the development and maintenance of neuropathic pain, ciRNA-Kat6b may be a potential new target for analgesic and treatment strategies. 相似文献77.
Bente Fjeld Åshild Amelie Sudmann-Day Runa Marie Grimholt Anne Cecilie Kjeldsen Larstorp Petter Urdal Olav Klingenberg 《International journal of laboratory hematology》2023,45(2):250-259
Introduction
The diagnosis of rare forms of α-thalassemia requires laborious genetic analyses. Accurate sample selection for such evaluation is therefore essential. The main objectives of this study were to investigate the predictive power of red blood cell parameters to detect rare forms of α-thalassemia (substudy 1), and to explore the frequency of rare versus common forms of α-thalassemia in our sample population (substudy 2).Methods
In substudy 1, we reviewed all blood samples selected for extended α-hemoglobinopathy evaluation at our laboratory during 2011–2020 (n = 1217), which included DNA sequencing and/or copy number variation analysis. We assessed α-thalassemia positive samples at different levels of mean corpuscular hemoglobin (MCH) alone and in combination with results for red blood cell count (RBC) or red cell distribution width (RDW). In substudy 2, we examined the distribution of α-thalassemia genotypes for all samples submitted to a first-tier hemoglobinopathy evaluation at our laboratory during 2014–2020 (n = 6495).Results
In substudy 1, both RBC and RDW added predictive value in detecting rare forms of α-thalassemia in samples from adults and children. In adult samples with MCH ≤ 23 pg, the presence of erythrocytosis increased the detection rate from 27% to 74% as compared to non-erythrocytosis, while normal RDW increased the detection rate from 36% to 86% as compared to elevated RDW. In substudy 2, rare forms of α-thalassemia were detected in 12% of α-thalassemia positive samples.Conclusion
Initial assessment of MCH, RBC, and RDW provided valuable predictive information about the presence of rare forms of α-thalassemia during hemoglobinopathy evaluation. 相似文献78.
79.
Chitra Basu Abhipriya Chatterjee Sampurna Bhattacharya Naibedya Dutta Runa Sur 《Experimental dermatology》2019,28(11):1328-1335
Tumor necrosis factor‐α (TNF‐α)‐induced keratinocyte inflammation plays a key role in the pathogenesis of multiple inflammatory skin diseases. Here we investigated the anti‐inflammatory effect of S‐allyl cysteine (SAC) on TNF‐α‐induced HaCaT keratinocyte cells and the mechanism behind its anti‐inflammatory potential. SAC was found to inhibit TNF‐α‐stimulated cytokine expression. Further, SAC was found to inhibit TNF‐α‐induced activation of p38, JNK and NF‐κB pathways. Interestingly, SAC was found to differentially regulate ERK MAP kinase in cells. TNF‐α‐induced transient ERK activation and SAC treatment resulted in sustained ERK activation both in the presence and absence of TNF‐α. Additionally, SAC failed to inhibit the TNF‐α‐induced expression of the pro‐inflammatory cytokines TNF‐α and IL‐1β when cells were treated with the MEK inhibitor PD98059, suggesting that the anti‐inflammatory effect of SAC is via sustained activation of the ERK pathway. Since ERK activation has been reported to negatively regulate NF‐κB‐driven gene expression and we find that SAC activates ERK and negatively regulates NF‐κB, we investigated whether there existed any crosstalk between the ERK and the NF‐κB pathways. NF‐κB‐dependent reporter assay, visualization of the nuclear translocation of NF‐κB‐p65 subunit and determination of the cellular levels of I‐κB, the inhibitor of NF‐κB, revealed that SAC inhibited TNF‐α‐induced NF‐κB activation, and PD98059 treatment reversed this effect. These results collectively suggest that SAC inhibits TNF‐α‐induced inflammation in HaCaT cells via a combined effect entailing the inhibition of the p38 and the JNK pathways and NF‐κB pathway via the sustained activation of ERK. 相似文献
80.
Martin K Sur R Liebel F Tierney N Lyte P Garay M Oddos T Anthonavage M Shapiro S Southall M 《Archives of dermatological research》2008,300(2):69-80
The skin is under continual assault from a variety of damaging environmental factors such as ultraviolet irradiation and atmospheric
pollutants, and as organisms age the cumulative damage exceeds the capacity of endogenous antioxidant defenses resulting in
chronic inflammation and premature aging. Botanical extracts such as Feverfew containing naturally occurring antioxidants
could replenish the depleted cutaneous stores and perhaps forestall these degenerative changes. A parthenolide-depleted extract
of Feverfew (PD-Feverfew), which was free of sensitization potential, was found to possess free radical scavenging activity
against a wide range of reactive oxygen species and with greater activity than Vitamin C. In vitro, PD-Feverfew restored cigarette
smoke-mediated depletion of cellular thiols, attenuated the formation of UV-induced hydrogen peroxide and reduced pro-inflammatory
cytokine release. In vivo, topical PD-Feverfew reduced UV-induced epidermal hyperplasia, DNA damage and apoptosis. In a clinical
study PD-Feverfew treatment significantly reduced erythema versus placebo 24 h post-UV exposure. Through the ability to scavenge
free radicals, preserve endogenous antioxidant levels, reduce DNA damage and induce DNA repair enzymes, which can help repair
damaged DNA, parthenolide-depleted extract of Feverfew may protect skin from the numerous external aggressions encountered
daily by the skin and reduce the damage to oxidatively challenged skin. 相似文献