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31.
Pekka Jousilahti Veikko Salomaa Katri Hakala Vesa Rasi Elina Vahtera Timo Palosuo 《Annals of allergy, asthma & immunology》2002,89(4):381-385
BACKGROUND: Airway inflammation is a characteristic feature of bronchial asthma. Previous studies have shown an increased local inflammatory activity in the airway mucosa of asthma patients. OBJECTIVES: To analyze the association of asthma with three sensitive markers of systemic inflammation, C-reactive protein, serum amyloid-A (SAA), and plasma fibrinogen. METHODS: A cross-sectional, population-based study including 1,513 Finnish men aged 45 to 74 years, who participated in a chronic disease risk factor survey in 1997. Of the participating men, 97 were classified as asthma patients. The odds ratios of asthma were analyzed by quartile of each inflammation marker. RESULTS: In logistic regression models the age-adjusted odds ratios (second, third, and fourth quartile as compared with the first quartile) of asthma increased gradually with increasing quartile of C-reactive protein (1.28, 1.19, 1.96, P for trend = 0.039), SAA (1.20, 3.00, 3.49, P for trend < 0.001), and fibrinogen (1.22, 1.79, 3.16, P for trend < 0.001). The associations were independent of smoking. Further adjustment for waist-to-hip ratio, a marker of central obesity, and symptoms of chronic bronchitis weakened the observed association, but the increasing trend in the association of SAA and fibrinogen with asthma remained highly significant. CONCLUSIONS: Sensitive markers of systemic inflammation, particularly SAA and fibrinogen, were positively and significantly associated with asthma prevalence. These findings support the hypothesis that not only local, but also systemic, inflammation exist in bronchial asthma. 相似文献
32.
Jukka Kemppainen Sargo Aalto Toshihiko Fujimoto Kari K. Kalliokoski Jaakko Långsjö Vesa Oikonen Juha Rinne Pirjo Nuutila Juhani Knuuti 《The Journal of physiology》2005,568(1):323-332
Physiological activation increases glucose uptake locally in the brain. However, it is not known how high intensity exercise affects regional and global brain glucose uptake. The effect of exercise intensity and exercise capacity on brain glucose uptake was directly measured using positron emission tomography (PET) and [18 F]fluoro-deoxy-glucose ([18 F]FDG). Fourteen healthy, right-handed men were studied after 35 min of bicycle exercise at exercise intensities corresponding to 30, 55 and 75% of on three separate days. [18 F]FDG was injected 10 min after the start of the exercise. Thereafter exercise was continued for another 25 min. PET scanning of the brain was conducted after completion of the exercise. Regional glucose metabolic rate (rGMR) decreased in all measured cortical regions as exercise intensity increased. The mean decrease between the highest and lowest exercise intensity was 32% globally in the brain (38.6 ± 4.6 versus 26.1 ± 5.0 μmol (100 g)−1 min−1 , P < 0.001). Lactate availability during exercise tended to correlate negatively with the observed brain glucose uptake. In addition, the decrease in glucose uptake in the dorsal part of the anterior cingulate cortex (37% versus 20%, P < 0.05 between 30% and 75% of ) was significantly more pronounced in subjects with higher exercise capacity. These results demonstrate that brain glucose uptake decreases with increase in exercise intensity. Therefore substrates other than glucose, most likely lactate, are utilized by the brain in order to compensate the increased energy needed to maintain neuronal activity during high intensity exercise. Moreover, it seems that exercise training could be related to adaptive metabolic changes locally in the frontal cortical regions. 相似文献
33.
Fasching PA Pharoah PD Cox A Nevanlinna H Bojesen SE Karn T Broeks A van Leeuwen FE van't Veer LJ Udo R Dunning AM Greco D Aittomäki K Blomqvist C Shah M Nordestgaard BG Flyger H Hopper JL Southey MC Apicella C Garcia-Closas M Sherman M Lissowska J Seynaeve C Huijts PE Tollenaar RA Ziogas A Ekici AB Rauh C Mannermaa A Kataja V Kosma VM Hartikainen JM Andrulis IL Ozcelik H Mulligan AM Glendon G Hall P Czene K Liu J Chang-Claude J Wang-Gohrke S Eilber U Nickels S Dörk T Schiekel M Bremer M 《Human molecular genetics》2012,21(17):3926-3939
Recent genome-wide association studies identified 11 single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. We investigated these and 62 other SNPs for their prognostic relevance. Confirmed BC risk SNPs rs17468277 (CASP8), rs1982073 (TGFB1), rs2981582 (FGFR2), rs13281615 (8q24), rs3817198 (LSP1), rs889312 (MAP3K1), rs3803662 (TOX3), rs13387042 (2q35), rs4973768 (SLC4A7), rs6504950 (COX11) and rs10941679 (5p12) were genotyped for 25 853 BC patients with the available follow-up; 62 other SNPs, which have been suggested as BC risk SNPs by a GWAS or as candidate SNPs from individual studies, were genotyped for replication purposes in subsets of these patients. Cox proportional hazard models were used to test the association of these SNPs with overall survival (OS) and BC-specific survival (BCS). For the confirmed loci, we performed an accessory analysis of publicly available gene expression data and the prognosis in a different patient group. One of the 11 SNPs, rs3803662 (TOX3) and none of the 62 candidate/GWAS SNPs were associated with OS and/or BCS at P<0.01. The genotypic-specific survival for rs3803662 suggested a recessive mode of action [hazard ratio (HR) of rare homozygous carriers=1.21; 95% CI: 1.09-1.35, P=0.0002 and HR=1.29; 95% CI: 1.12-1.47, P=0.0003 for OS and BCS, respectively]. This association was seen similarly in all analyzed tumor subgroups defined by nodal status, tumor size, grade and estrogen receptor. Breast tumor expression of these genes was not associated with prognosis. With the exception of rs3803662 (TOX3), there was no evidence that any of the SNPs associated with BC susceptibility were associated with the BC survival. Survival may be influenced by a distinct set of germline variants from those influencing susceptibility. 相似文献
34.
Antidepressants protect against hippocampal volume loss in humans and reverse stress-induced atrophic changes in animals thus supporting the hypothesis that the pathophysiology of stress-related disorders such as depression involves reductions in neuronal connectivity and this effect is reversible by antidepressant treatment. However, it is unclear which brain areas demonstrate such alterations in plasticity in response to antidepressant treatment. The aim of the present study was to examine the effect of antidepressant treatment on the expression of three plasticity-associated marker proteins, the polysialylated form of nerve cell adhesion molecule (PSA-NCAM), phosphorylated cyclic-AMP response element binding protein (pCREB) and growth-associated protein 43 (GAP-43), in the rat brain. To this end, rats were treated either acutely (60 min) or chronically (21 days) with imipramine (30 and 15 mg/kg, respectively) and the expression of PSA-NCAM, pCREB, and GAP-43 was assessed using immunohistochemistry. Initial mapping revealed that chronic imipramine treatment increased expression of these plasticity-associated proteins in the hippocampus, medial prefrontal cortex and piriform cortex but not in the other brain regions examined. Since PSA-NCAM and pCREB are expressed in recently-generated neurons in the dentate gyrus, it is likely that chronic imipramine treatment increased their expression in the hippocampus at least partially by increasing neurogenesis. In contrast, since chronic imipramine treatment is not associated with neurogenesis in the medial prefrontal cortex, increased expression of PSA-NCAM and pCREB in the prelimbic cortex implicates changes in synaptic connectivity in this brain region. Acute treatment with imipramine increased the number of pCREB positive nuclei in the hippocampus and the prefrontal cortex but did not alter expression of GAP-43 or PSA-NCAM in any of the brain regions examined. Taken together, the results of the present study suggest that antidepressant treatment increases synaptic plasticity and connectivity in brain regions associated with mood disorders. 相似文献
35.
Kivinen K Peterson H Hiltunen L Laivuori H Heino S Tiala I Knuutila S Rasi V Kere J 《European journal of human genetics : EJHG》2007,15(4):494-497
Preeclampsia is a common, pregnancy-specific vascular disorder characterised by hypertension and proteinuria. A recent report suggested association of the STOX1 gene on chromosome 10q22.1 with preeclampsia in the Dutch population. Here, we present a comprehensive assessment of STOX1 as a candidate gene for preeclampsia in the Finnish population by re-examining our previous genetic linkage analysis results for both chromosome 10 and paralogous loci, by genotyping representative markers in a nationwide data set, and by studying STOX1 expression in placentas from preeclamptic and uncomplicated pregnancies. In conclusion, we are unable to validate STOX1 as a common preeclampsia susceptibility gene. 相似文献
36.
Population-based study of salivary carriage of periodontal pathogens in adults 总被引:1,自引:1,他引:1 下载免费PDF全文
Könönen E Paju S Pussinen PJ Hyvönen M Di Tella P Suominen-Taipale L Knuuttila M 《Journal of clinical microbiology》2007,45(8):2446-2451
Large, general population-based data on carriage rates of periodontal pathogens hardly exist in the current literature. The objectives of the present study were to examine the salivary detection of Aggregatibacter (formerly Actinobacillus) actinomycetemcomitans, Campylobacter rectus, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythensis, and Treponema denticola in a representative sample of the adult population living in southern Finland and to clarify which determinants are associated with the presence of these pathogens in saliva. 16S rRNA-based PCR methods with species-specific primers were employed to determine the presence of the six target bacteria in stimulated saliva samples, which were available from 1,294 subjects aged > or =30 years. The age group, gender, level of education, marital status, smoking history, number of teeth, and number of teeth with deepened pockets were included in the statistical analysis. In general, the carriage of periodontal pathogens was common, since at least one of the examined pathogens was found in 88.2% of the subjects. In descending order, the total detection rates were 56.9%, 38.2%, 35.4%, 31.3%, 20.0%, and 13.9% for T. forsythensis, T. denticola, P. gingivalis, C. rectus, A. actinomycetemcomitans, and P. intermedia, respectively. Age per se was strongly associated with the carriage of P. gingivalis (P = 0.000), and the level of education with that of T. denticola (P = 0.000). There was an association between the number of teeth with deepened pockets and carriage of P. gingivalis (P = 0.000), P. intermedia (P = 0.000), T. denticola (P = 0.000), and A. actinomycetemcomitans (P = 0.004). The data suggest that distinct species have a different carriage profile, depending on variables such as age, educational level, and periodontal status. 相似文献
37.
Mika Pulkkinen Jere Pikkarainen Thomas Wirth Tommy Tarvainen Vesa Haapa-Aho Harri Korhonen Jukka Sepp?l? Kristiina J?rvinen 《European journal of pharmaceutics and biopharmaceutics》2008,70(1):66-74
Despite recent advances in cancer therapy, many malignant tumors still lack effective treatment and the prognosis is very poor. Paclitaxel is a potential anticancer drug, but its use is limited by the facts that paclitaxel is a P-gp substrate and its aqueous solubility is poor. In this study, three-step tumor targeting of paclitaxel using biotinylated PLA-PEG nanoparticles and avidin-biotin technology was evaluated in vitro as a way of enhancing delivery of paclitaxel. Paclitaxel was incorporated both in biotinylated (BP) and non-biotinylated (LP) PEG-PLA nanoparticles by the interfacial deposition method. Small (mean size approximately 110nm), spherical and slightly negatively charged (-10mV) BP and LP nanoparticles achieving over 90% paclitaxel incorporation were obtained. The successful biotinylation of nanoparticles was confirmed in a novel streptavidin assay. BP nanoparticles were targeted in vitro to brain tumor (glioma) cells (BT4C) by three-step avidin-biotin technology using transferrin as the targeting ligand. The three-step targeting procedure increased the anti-tumoral activity of paclitaxel when compared to the commercial paclitaxel formulation Taxol((R)) and non-targeted BP and LP nanoparticles. These results indicate that the efficacy of paclitaxel against tumor cells can be increased by this three-step targeting method. 相似文献
38.
Production and characterisation of monoclonal antibodies against a very small hapten, 3-methylindole
Tuomola M Harpio R Mikola H Knuuttila P Lindström M Mukkala VM Matikainen MT Lövgren T 《Journal of immunological methods》2000,240(1-2):111-124
Monoclonal antibodies were produced against a very small (131.2 Da) hapten, 3-methylindole. Nine derivatives of 3-methylindole were synthesised with spacers ending in a carboxyl group, and coupled to immunogenic carriers and europium chelate labels. Almost all the antigens elicited an antihapten response, but the majority of the mAbs produced strongly recognised the spacer group and did not bind free 3-methylindole. However, specific antibodies were obtained with five immunogens. Specificity could be directed against the pyrrole ring by locating the bridging group to the aromatic moiety of the indole ring system. Any modification in the position 3 of the indole ring strongly hindered mAb binding to the compound, and the cross-reactivity of physiologically important compounds, such as tryptophan and tryptamine, was negligible for all of the mAbs. The developed hapten structures successfully focused antibody recognition to the important sub-determinants in the indole ring system. Similar constructs could also be useful in the development of antibodies against other indolic compounds. 相似文献
39.
Kaasinen V Någren K Järvenpää T Roivainen A Yu M Oikonen V Kurki T Rinne JO 《Journal of clinical psychopharmacology》2002,22(6):615-620
Donepezil and rivastigmine are acetylcholinesterase (AChE) inhibitors used to improve cholinergic neurotransmission and cognitive function in Alzheimer's disease (AD). This study examined direct effects of these drugs on AChE activity in the frontal, temporal, and parietal cortices in AD. Six AD patients were scanned with positron emission tomography before and after 3 months of treatment with donepezil (10 mg/day), and five AD patients were scanned before and after 3 to 5 months of treatment with rivastigmine (9 mg/day). Healthy unmedicated controls were imaged twice to evaluate the reproducibility of the method. A specific AChE tracer, [methyl-11C]N-methyl-piperidyl-4-acetate, and a 3D positron emission tomography system with MRI coregistration were used for imaging. Treatment with donepezil reduced the AChE activity (k3 values) in the AD brain by 39% in the frontal (p < 0.001, Bonferroni corrected), 29% in the temporal (p = 0.02, corrected) and 28% in the parietal cortex (p = 0.05, corrected). The corresponding levels of inhibition for rivastigmine were 37% (p = 0.003, corrected), 28% (p = 0.03, uncorrected) and 28% (p = 0.05, corrected). When the treatment groups were combined, the level of AChE inhibition was significantly greater in the frontal cortex compared to the temporal cortex (p = 0.03, corrected). The test-retest analysis with healthy subjects indicated good reproducibility for the method, with a nonsignificant 0% to 7% intrasubject variability between scans. The present study provides first evidence for the effect of rivastigmine on cortical AChE activity. Our results indicate that the pooled effects of donepezil and rivastigmine on brain AChE are greater in the frontal cortex compared to the temporal cortex in AD. This regional difference is probably related to the prominent temporoparietal reduction of AChE in AD. We hypothesize that the clinical improvement in behavioral and attentional symptoms of AD due to AChE inhibitors is associated with the frontal AChE inhibition. 相似文献
40.
Mäkitie A Pirvola U Pyykkö I Sakakibara H Riihimäki V Ylikoski J 《Archives of toxicology》2002,76(1):40-47
The effect of inhaled styrene on the structure and function of the auditory organ of the male Wistar rat was studied. The animals were exposed either to 600, 300 or 100 ppm styrene (12 h/day, 5 days/week, for 4 weeks). Auditory sensitivity was tested prior to and after the exposure by auditory brain stem audiometry (ABR) at frequencies of 1.0, 2.0, 4.0 and 8.0 kHz. Inner ear morphological changes were studied by light- and electron-microscopy. Exposure to 600 ppm styrene caused a 3 dB hearing loss only at the highest test frequency (8 kHz). Quantitative morphological analysis of cochlear hair cells (cytocochleograms) showed that 600 ppm styrene caused a severe outer hair cell (OHC) loss particularly in the third OHC row of the upper basal and lower middle coil. The inner hair cells were usually intact. Exposure to lower styrene concentrations (100 and 300 ppm) caused no unequivocal functional deficit or hair cell damage. We conclude that there appears to be a concentration threshold for styrene ototoxicity in rats (between 300 and 600 ppm). 相似文献