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1.
The contribution of the cerebrospinal fluid-contacting nucleus (CSF-contacting nucleus) and adrenomedullin (ADM) to the developmental modulation of stressful events remains controversial. This study explored the effects of endogenous ADM in the CSF-contacting nucleus on immobilization of stress-induced physiological parameter disorders and glucocorticoid hormone releasing hormone (CRH), rat plasma corticosterone expression, and verification of such effects by artificially lowering ADM expression in the CSF-contacting nucleus by targeted ablation of the nucleus. Immunohistochemical experiments showed that ADM-like immunoreactivity and the calcitonin receptor-like receptor (CRLR) marker were localized in the CSF-contacting nucleus. After 7 continuous days of chronic immobilization stress (CIS), animals exhibited anxiety-like behavior. Also, an increase in serum corticosterone, and enhanced expression of ADM in the CSF-contacting nucleus were observed, following activation by CIS. The intracerebroventricular (i.c.v.) administration of the ADM receptor antagonist AM22–52 significantly reduced ADM in the CSF-contacting nucleus, additionally, blocked the effects of ADM, meaning the expression of CRH in the hypothalamic paraventricular nucleus (Pa) and serum corticosterone level were increased, and the physiological parameters of the rats became correspondingly deteriorated. Additionally, the i.c.v. administration of cholera toxin subunit B-saporin (CB-SAP), a cytotoxin coupled to a cholera toxin subunit, completely eliminated the CSF-contacting nucleus, worsening the reaction of the body to CIS. The collective results demonstrated that ADM acted as a stress-related peptide in the CSF-contacting nucleus, and its lower expression and blocked effects in the nucleus contributed to the deterioration of stress-induced physiologic parameter disorders as well as the excessive expressions of stress-related hormones which were part of the hypothalamic–pituitary–adrenal (HPA) axis.  相似文献   
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In this study, we clarified the gender and age-related asymmetries of the central sulcus (CS) in early adulthood using a parametric ribbon method. The CS was reconstructed and parameterized automatically from 3D MR images of 112 healthy right-handed subjects. The 3D anatomic morphology of the CS was presented using 5 sulcal parameters, including sulcal depth position-based profile (DPP), average depth (AD), average width (AW), top length (TL) and bottom length (BL). Asymmetry differences in DPPs were found in the medial and lateral part of the CS. In addition, significant gender differences were observed in the medial and middle parts of the right CS DPPs but scattered in the left side. We found leftward asymmetries of TL in males, but rightward asymmetries of AW in females. Males had a greater AW than females in the right hemisphere. Moreover, the females had bilateral longer TL and a longer left BL than did males. We also found significant age-related reductions in bilateral TL and increases in bilateral AW, with males presenting more obvious age-related change than females. There were sexual differences of the CS patterns, in which Type b was the most dominant sulcal pattern in males, whereas Type a was dominant in females. Three-way ANOVA revealed sexual and asymmetry changes of TL and BL among different CS patterns. Our findings indicate that the lateralization performances of the CS manifest as sexually and regionally different. In addition, it is suggested that males may undergo a faster progress of aging compared to females.  相似文献   
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Nine novel 4‐aminoquinazoline derivatives were designed and synthesized. Biochemical and cellular analyses demonstrated that most of the derivatives exhibited a strong activity to inhibit Aurora A and B kinases and to suppress the proliferation of a panel of human tumor cell lines (U937, K562, A549, LoVo, and HT29). Quantum chemical studies were also carried out to determine the structural features of these compounds engaged in the inhibition of Aurora kinases.  相似文献   
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As malignant neoplasm is a major public health problem, there is a need for the development of a novel modulator that enhances antitumor activity and reduces adverse reactions to antitumor agents. In this study, the effects of some volatile oil components in Humulus lupulus on doxorubicin (DOX) permeability in tumor cells and DOX-induced antitumor activity were examined. In vitro, DOX levels in tumor cells by combined linalool as its component significantly increased in the DOX influx system, and the increased effect by linalool on DOX cytotoxicity was shown. In vivo, the combination of DOX with linalool significantly decreased tumor weight compared with that of DOX alone treated group. The promotion of DOX influx level by combined linalool did not depend on energy, whereas it was suppressed by the absence of Na+. This promoting effect was suppressed by the presence of S-(4-nitrobenzyl)-6-thioinosine and inhibited dependently on phlorizin concentration. It is considered that linalool promoted DOX influx in tumor cells because of its action on DOX transport through concentrative Na+-dependent nucleoside transporter 3, which increased DOX concentration in tumor cells and thus enhanced the antitumor activity of DOX. Therefore, linalool as a food component is anticipated to be an effective DOX modulator.  相似文献   
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《Medical hypotheses》2013,80(6):819-822
Amyotrophic lateral sclerosis (ALS) is thought to be due to primary involvement of motor neurons. Pathogenic mechanisms underlying its appearance are relatively well known and include inflammation, excitotoxicity, oxidative stress, endoplasmic reticulum stress, protein damage, genetic abnormalities and type of neuronal death. Although these processes have been investigated in detail in the past two decades none of them appear to be the cause of the illness. In addition several possible environmental agents have been investigated but the results, in every case, were conflicting and therefore inconclusive. However, since the motor neurons display the features of apoptosis in this illness, the possibility remains that the motor neurons die because of a hostile environment, one that is unable to sustain their health, rather than being directly targeted themselves.The above considerations lead to an examination of astrocytes, for these cells play a key role in controlling the environment of neurons. It is known that astrocytes are exquisitely plastic, adapting their metabolism and behaviour to the needs of the neurons they contact. Each population of astrocytes is therefore unique and, were one to be adversely affected at the start of a disease process, the consequences would extend to the neurons that it normally chaperoned. The disturbed relationship might involve inappropriate production and secretion of astrocytic neurotransmitters, defective transport of glutamate and impaired trophic and metabolic support of the motor neurons.In order to explain the spread of weakness and pyramidal signs in ALS patients, which is very often from one group of muscles to a neighbouring one, it is postulated that, within the spinal cord, the brainstem and the motor cortex, the disease-causing process is also spreading—in this case, from one group of astrocytes to its neighbours. A misfolded protein, possibly a prion-like protein, would be a candidate for this type of transmission.  相似文献   
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Several combinations of inflammatory factors, including neutrophil-to- lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), have been reported to be prognostic factors in various malignant tumors, including colorectal cancer (CRC). The aim of this study was to evaluate the prognostic value of NLR and PLR for patients with rectal cancer (RC) who underwent curative surgery. Data from patients who underwent curative resection for RC were retrospectively reviewed. The cutoff for NLR and PLR was defined as 2.3 and 144 by receiver operating characteristic (ROC) curve. Overall survival (OS) and disease-free survival (DFS) were assessed using Kaplan-Meier method. Multivariable Cox regression model was used to evaluate the independent prognostic significance of variables. A total of 140 patients were eligible in the study. High NLR (> 2.3) and high PLR (> 144) both predicted lower OS and DFS according to Kaplan-Meier method. But in the multivariable Cox regression model, only the high NLR retained significance for reduced OS and DFS. According to Chi-square test, patients with higher NLR had larger tumor size and higher pN-stage. While PLR was only associated with the pN-stage. High preoperative NLR was shown to be a negative independent prognostic factor in patients undergoing resection for nonmetastatic RC. It may be helpful as a factor to guide the postoperative therapies.  相似文献   
9.
An immunosuppressant with fewer adverse effects is still urgently needed for increasing numbers of patients suffering from allergic contact dermatitis. In the present study, we aimed to investigate the immunosuppressive activity of herpetol on T-lymphocytes in vitro and in vivo and explore its potential pharmacological mechanism. The results showed that herpetol could effectively inhibit the proliferation of activated T cells and reduce the production of pro-inflammatory cytokines at 5–20 μM. Additionally, the ear swelling and inflammatory responses induced by picryl chloride were significantly ameliorated by herpetol at 20–40 mg/kg. Moreover, herpetol could cause cell cycle arrest of activated T cells in a dose-dependent manner. Furthermore, herpetol reduced the expression and activity of HIF-1α, Glut1 and LDHA, leading to glycolysis inhibition in activated T cells. Taken together, herpetol showed an immunosuppressive activity against T-cell mediated immune responses in vitro and in vivo, and it has potential for the treatment of immune-related skin diseases.  相似文献   
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