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71.
A Amoruso G Gunella E Rondano C Bardelli LG Fresu V Ferrero F Ribichini C Vassanelli S Brunelleschi 《British journal of pharmacology》2009,158(5):1276-1284
Background and purpose:
Tobacco smoke represents a relevant risk factor for coronary heart disease (CHD). Although peroxisome proliferator-activated receptor (PPAR)γ activation reduces inflammation and atherosclerosis, expression of PPARγ in cells and its modulation by smoking are poorly investigated. We previously reported that monocyte/macrophages from healthy smokers exhibited an enhanced constitutive expression of PPARγ. Here, we evaluated PPARγ expression and basal cytokine release in monocytes and monocyte-derived macrophages (MDMs) from 85 CHD patients, classified by their smoking habit (smokers, non-smokers and ex-smokers), and assessed the role of PPARγ ligands in this context.Experimental approach:
PPARγ protein was detected by Western blot and semi-quantified by PPARγ/β-actin ratio; cytokine release was measured by elisa and nuclear factor-kappaB (NF-κB) translocation by electrophoretic mobility shift assays.Key results:
As compared to the other groups, MDMs from smoker CHD patients exhibited a reduced PPARγ/β-actin ratio and an increased spontaneous release of tumour necrosis factor-α (TNF-α) and interleukin-6, but with no major variations in monocytes. In cells from selected CHD patients, rosiglitazone inhibited TNF-α release and NF-κB translocation induced by phorbol-12-myristate 13-acetate. The selective PPARγ antagonist GW9662 reversed these effects, with some variations related to smoking habit.Conclusions and implications:
In CHD patients, exposure to tobacco smoke profoundly affected PPARγ expression, and this was related to levels of secretion of pro-inflammatory cytokines. MDMs from CHD smokers showed the lowest PPARγ expression and released more inflammatory cytokines. Moreover, rosiglitazone''s ability to inhibit cytokine release and its reversal by GW9662 clearly indicated PPARγ involvement in these changes in CHD patients. 相似文献72.
Genetic variability in nicotinic acetylcholine receptors and nicotine addiction: converging evidence from human and animal research 总被引:1,自引:0,他引:1
Tobacco smoking is a leading preventable cause of death in the United States and produces a major health and economic burden. Although the majority of smokers want to quit, few are successful. These data highlight the need for additional research into the neurobiology of tobacco dependence. Addiction to nicotine, the main psychoactive component of tobacco, is influenced by multiple factors that include individual differences in genetic makeup. Twin studies have demonstrated that genetic factors can influence vulnerability to nicotine addiction, and subsequent research has identified genes that may alter sensitivity to nicotine. In humans, genome-wide and candidate gene association studies have demonstrated that genes encoding nicotinic acetylcholine receptor (nAChR) proteins are associated with multiple smoking phenotypes. Similarly, research in mice has provided evidence that naturally occurring variability in nAChR genes is associated with changes in nicotine sensitivity. Furthermore, the use of genetic knockout mice has allowed researchers to determine the nAChR genes that mediate the effects of nicotine, whereas research with knockin mice has demonstrated that changes to nAChR genes can dramatically alter nicotine sensitivity. This review will examine the genetic factors that alter susceptibility to nicotine addiction, with an emphasis on the genes that encode nAChR proteins. 相似文献
73.
Multidrug-resistance protein 1 (MRP-1) confers resistance to a number of clinically important chemotherapeutic agents. The promoter of the mrp-1 gene contains an Sp1-binding site, which we targeted using the antitumor bis-anthracycline WP631. When MCF-7/VP breast cancer cells, which overexpress MRP-1 protein, were incubated with WP631 the expression of the multidrug-resistance protein gene decreased. Conversely, doxorubicin did not alter mrp-1 gene expression. The inhibition of gene expression was followed by a decrease in the activity of the MRP-1 protein. The IC(75) for WP631 (drug concentration required to inhibit cell growth by 75%) circumvented the drug-efflux pump, without addition of resistant modifiers. After treatment with WP631, MCF-7/VP cells were committed to die after entering mitosis (mitotic catastrophe), while treatment with doxorubicin did not affect cell growth. This is the first report on an antitumor drug molecule inhibiting the mrp-1 gene directly, rather than being simply a poor substrate for the transporter-mediated efflux. However, both situations appeared to coexist, thereby a superior cytotoxic effect was attained. Ours results suggest that WP631 offers great potential for the clinical treatment of tumors displaying a multidrug-resistance phenotype. 相似文献
74.
Juan Rodríguez‐Silverio Myrna Déciga‐Campos Gerardo Reyes‐García Miriam del Carmen Carrasco‐Portugal Francisco J. Flores‐Murrieta 《Drug development research》2011,72(5):391-396
Diclofenac and tramadol are drugs widely used for the treatment of pain. However, side effects may limit their use. As both drugs produce side effects that are dose‐dependent, it seems appropriate to combine them in order to reduce the requirements for efficacy and, consequently, side effects. The purpose of this study was to evaluate the possible synergistic effect of these drugs in three experimental models of nociception in the rat. Dose‐response curves for diclofenac and tramadol were constructed in three models, thermal hyperalgesia, formalin, and hot plate. From these curves, ED40 or ED30 (according to the model employed) values were obtained and isobolographic analyses were carried out based on 0.5:0.5 proportions. Synergistic interactions were observed in the thermal hyperalgesia and hot plate models and an additive interaction was obtained in the formalin test. These results suggest a good therapeutic potential of this combination in the treatment of pain. Drug Dev Res 72: 391–396, 2011. © 2011 Wiley‐Liss, Inc. 相似文献
75.
LG Essen 《MedR Medizinrecht》2002,20(6):311-313
Ohne Zusammenfassung 相似文献
76.
LG Hannover 《MedR Medizinrecht》2000,18(2):88-89
Ohne Zusammenfassung 相似文献
77.
M Blessmann Weber† LG Sponchiado de Ávila‡ R Albaneze‡ OL Magalhães de Oliveira§¶ BD Sudhaus¶ T Ferreira Cestari§ 《Journal of the European Academy of Dermatology and Venereology》2002,16(5):463-468
BACKGROUND: The aetiology of pityriasis alba (PA), a common dermatosis in childhood, is still controversial. The objective of this study was to assess the possible aetiopathogenic factors of this disease in infants. METHODS: Forty-four patients with PA and 31 healthy children were examined and compared. Personal hygiene habits, sun exposure, presence of Staphylococcus aureus in nasal fossae and presence of major or minor signs of atopy were assessed during anamnesis and physical examination. Susceptibility to ultraviolet (UV) B radiation was measured by the onset of a contact hypersensitivity reaction to diphenylcyclopropenone in individuals sensitized in previously irradiated areas. RESULTS: The prevalence of PA was higher in individuals with darker skin, in high phototype categories, as well as in males. The number of daily baths and sun exposure between 10.00 h and 15.00 h were significantly higher in the PA group when compared with controls (P = 0.03 and P = 0.0015, respectively). The presence of atopy signs was more common in pityriasis patients (P = 0.002). Susceptibility to UVB radiation was 29.6% in the PA group vs. 29.0% in the control group; nevertheless, important differences were found after stratification in order to control possible confounding factors. The presence of S. aureus in the nostrils was equal in both groups. CONCLUSIONS: Our results confirm that PA, in our population, is more prevalent in males and in individuals in higher phototype categories. In those with inadequate personal hygiene and sun exposure habits the disease is more accentuated, demonstrating that the xerosis presenting in individuals with atopic diathesis is an important element in the development of the disease. S. aureus is not an important aetiopathogenic factor in PA. Susceptibility to UVB becomes important when related to the patient's phototype. 相似文献
78.
J. Brayer P. Brunet J. J. Sampol . Brottier A. M. Lorec-Penet J. Mancini X. Thirion H. Portugal Y. Berland 《ITBM》2003,24(4):192-198
Heparinisation of the extracorporal circuit in hemodialysis is particularly difficult to perform in patients at risk of haemorrhage. Excessive doses may provoke bleeding and insufficient doses may lead to clotting in the tubing. Both an adequate initial bolus of heparin and appropriate adjustment during the dialysis session is critical. Although the lines and the dialyser are systematically controlled clinically, at present, no biological parameter is used. The delay before obtaining a result from the laboratory is too long to enable a rapid and effective modification in the anticoagulant dose. A bedside coagulation monitoring, i.e. which can be used in the department itself, might be the solution. Gamida distributes 2 Hemochron® monitors, which measure whole blood coagulation time (activated clotting time ACT). We tested each of these monitors, with regard to their handling and the results that they supplied. Eleven patients were included. Regular measurements of ACT were performed during the session simultaneously with each of the Hemochrons. The results obtained were then compared in parallel with the measurements of TCA and heparinisation supplied by the laboratory. Both of the Hemochron monitors provided satisfactory results, but it was the practical assessment that oriented our conclusions. The economical aspects of this type of material are under assessment. 相似文献
79.
Viveiros M Portugal I Bettencourt R Victor TC Jordaan AM Leandro C Ordway D Amaral L 《Antimicrobial agents and chemotherapy》2002,46(9):2804-2810
An American Type Culture Collection reference strain and eight clinical strains of Mycobacterium tuberculosis, all of which were susceptible to isoniazid (INH) (mean MIC, 0.06 mg/liter) and negative for the Ser315Thr katG mutation, were left in their BACTEC 12B vials (for use with the BACTEC 460-TB method) containing 0.1 mg of INH per liter for periods of up to 28 days after the completion of the antibiotic susceptibility test. Each eventually grew to levels compatible with those of INH-resistant strains. Successive passages in INH-containing BACTEC 12B vials and onto solid media showed that the resistance noted above was maintained. Successive passages of these M. tuberculosis strains in which INH resistance had been induced into BACTEC 12B vials or solid media containing stepwise increases in INH concentrations eventually yielded organisms resistant to 20 mg of INH per liter. Transfer of cells in which INH resistance had been induced to drug-free medium followed by repeated passages in that medium eventually yielded organisms whose susceptibility to INH was identical to that of the original parent strains. The cycle of induced INH resistance could be repeated with these now INH-susceptible cells. The use of M. tuberculosis identification probes and IS6110-based restriction fragment length polymorphism analyses of cultures throughout the induction of INH resistance and the reversal of resistance in drug-free medium eliminated the possibility that the culture was contaminated or that the initial specimen had a mixed type of infection. Induced high-level resistance to INH (20 mg/liter) could be reduced 100-fold with a subinhibitory concentration of reserpine but not with verapamil. These results collectively suggest that high-level resistance to INH can be induced in INH-susceptible M. tuberculosis strains by the induction of a reserpine-sensitive efflux mechanism. 相似文献
80.
L Laval R Martin JN Natividad F Chain S Miquel C Desclée de Maredsous S Capronnier H Sokol EF Verdu JET van Hylckama Vlieg LG Bermúdez-Humarán T Smokvina P Langella 《Gut microbes》2015,6(1):1-9
Impaired gut barrier function has been reported in a wide range of diseases and syndromes and in some functional gastrointestinal disorders. In addition, there is increasing evidence that suggests the gut microbiota tightly regulates gut barrier function and recent studies demonstrate that probiotic bacteria can enhance barrier integrity. Here, we aimed to investigate the effects of Lactobacillus rhamnosus CNCM I-3690 on intestinal barrier function. In vitro results using a Caco-2 monolayer cells stimulated with TNF-α confirmed the anti-inflammatory nature of the strain CNCM I-3690 and pointed out a putative role for the protection of the epithelial function. Next, we tested the protective effects of L. rhamnosus CNCM I-3690 in a mouse model of increased colonic permeability. Most importantly, we compared its performance to that of the well-known beneficial human commensal bacterium Faecalibacterium prauznitzii A2-165. Increased colonic permeability was normalized by both strains to a similar degree. Modulation of apical tight junction proteins expression was then analyzed to decipher the mechanism underlying this effect. We showed that CNCM I-3690 partially restored the function of the intestinal barrier and increased the levels of tight junction proteins Occludin and E-cadherin. The results indicate L. rhamnosus CNCM I-3690 is as effective as the commensal anti-inflammatory bacterium F. prausnitzii to treat functional barrier abnormalities. 相似文献