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排序方式: 共有260条查询结果,搜索用时 11 毫秒
1.
Jean-Franois Rual Tomoko Hirozane-Kishikawa Tong Hao Nicolas Bertin Siming Li Amlie Dricot Ning Li Jennifer Rosenberg Philippe Lamesch Pierre-Olivier Vidalain Tracey R. Clingingsmith James L. Hartley Dominic Esposito David Cheo Troy Moore Blake Simmons Reynaldo Sequerra Stephanie Bosak Lynn Doucette-Stamm Christian Le Peuch Jean Vandenhaute Michael E. Cusick Joanna S. Albala David E. Hill Marc Vidal 《Genome research》2004,14(10B):2128-2135
The advent of systems biology necessitates the cloning of nearly entire sets of protein-encoding open reading frames (ORFs), or ORFeomes, to allow functional studies of the corresponding proteomes. Here, we describe the generation of a first version of the human ORFeome using a newly improved Gateway recombinational cloning approach. Using the Mammalian Gene Collection (MGC) resource as a starting point, we report the successful cloning of 8076 human ORFs, representing at least 7263 human genes, as mini-pools of PCR-amplified products. These were assembled into the human ORFeome version 1.1 (hORFeome v1.1) collection. After assessing the overall quality of this version, we describe the use of hORFeome v1.1 for heterologous protein expression in two different expression systems at proteome scale. The hORFeome v1.1 represents a central resource for the cloning of large sets of human ORFs in various settings for functional proteomics of many types, and will serve as the foundation for subsequent improved versions of the human ORFeome. 相似文献
2.
Karine Titier Pierre-Olivier Girodet Hélène Verdoux Mathieu Molimard Bernard Bégaud Wilhelm Haverkamp Malcolm Lader Nicholas Moore 《Drug safety》2005,28(1):35-51
Syncope and sudden death are features of schizophrenia that can be attributed to ischaemic heart disease, the use of antipsychotics (because of proarrhythmia or other reasons such as pharyngeal dyskinesia) or the psychiatric disease itself. Cases have been described with most antipsychotics and have led to the withdrawal, temporary suspension from the market or restricted use of antipsychotics, such as sultopride, droperidol, sertindole or thioridazine. Reviewing the available data shows that all antipsychotics tested affect the cardiac potassium channel, with the concentration that produces 50% inhibition (IC50) ranging from 1 nmol/L (haloperidol) to 6 micromol/L (olanzapine). Experimental in vitro or in vivo electrophysiological studies have shown a dose-dependent increase in the duration of the action potential with various degrees of indicators of serious arrhythmogenicity. However, this does not always translate clinically into an increased duration of the QT interval or increased risk of torsade de pointes or sudden death in clinical trials or pharmacoepidemiological studies. In turn, QT prolongation in clinical trials does not always translate to an increased risk of torsade de pointes or sudden death. The reasons for these apparent discrepancies are unclear and could be related to insufficiently powered field studies, low plasma and tissue drug concentrations with reference to in vitro data or drug effects on other receptors or ion channels that have a protective effect. Alternatively, risks that were not apparent from preclinical or clinical data could be related to the use of the drug in high-risk patients, metabolic interactions or other factors that would only be encountered in large postmarketing populations. The assessment of cardiovascular safety, both preclinical and during premarketing clinical trials, needs to be supported by appropriately powered pharmacoepidemiology studies. 相似文献
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Oppliger A Rusca S Charrière N Vu Duc T Droz PO 《The Annals of occupational hygiene》2005,49(5):385-391
An assessment of wood workers' exposure to airborne cultivable bacteria, fungi, inhalable endotoxins and inhalable organic dust was performed at 12 sawmills that process mainly coniferous wood species. In each plant, samples were collected at four or five different work sites (debarking, sawing, sorting, planing and sawing cockpit) and the efficiency of sampling devices (impinger or filter) for determining endotoxins levels was evaluated. Results show that fungi are present in very high concentrations (up to 35 000 CFU m(-3)) in all sawmills. We also find that there are more bioaerosols at the sorting work site (mean +/- SD: 7723 +/- 9919 CFU m(-3) for total bacteria, 614 +/- 902 CFU m(-3) for Gram-negative, 19 438 +/- 14 246 CFU m(-3) for fungi, 7.0 +/- 9.0 EU m(-3) for endotoxin and 2.9 +/- 4.8 g m(-3) for dust) than at the sawing station (mean +/- SD: 1938 +/- 2478 CFU m(-3) for total bacteria, 141 +/- 206 CFU m(-3) for Gram-negative, 12 207 +/- 10 008 CFU m(-3) for fungi, 2.1 +/- 1.9 EU m(-3) for endotoxin and 0.75 +/- 0.49 mg m(-3) for dust). At the same time, the species composition and concentration of airborne Gram-negative bacteria were studied. Penicillinium sp. were the predominant fungi, while Bacillus sp. and the Pseudomonadacea family were the predominant Gram-positive and Gram-negative bacteria encountered, respectively. 相似文献
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Amb a 1-immunostimulatory oligodeoxynucleotide conjugate immunotherapy decreases the nasal inflammatory response 总被引:9,自引:0,他引:9
Tulic MK Fiset PO Christodoulopoulos P Vaillancourt P Desrosiers M Lavigne F Eiden J Hamid Q 《The Journal of allergy and clinical immunology》2004,113(2):235-241
BACKGROUND: Amb a 1-immunostimulatory phosphorothioate oligonucleotide conjugate (AIC) is a novel immunotherapeutic compound consisting of purified Amb a 1 from short ragweed proteins covalently linked to an immunostimulatory phosphorothioate oligodeoxyribonucleotide. In sensitized animals AIC can stimulate an Amb a 1-specific T(H)1 response and decrease pulmonary reactivity to ragweed challenge. Clinical trials have documented reduced allergic response to AIC in comparison with licensed ragweed extract. OBJECTIVES: We sought to determine the in vivo effect of short-course immunotherapy with AIC on eosinophilia and cytokine mRNA expression in the nasal mucosa of ragweed-sensitive patients. METHODS: Ragweed-sensitive patients with allergic rhinitis were treated with 6 escalating doses of AIC (0.06-12 microg, n = 28) or placebo (n = 29) at weekly intervals immediately before the 2001 ragweed season. Symptom scores and medication use were recorded for the 2001 and 2002 ragweed seasons for all patients. A subset of patients (12 receiving AIC and 7 receiving placebo) consented to have nasal biopsy specimens taken before immunization and before and after the first ragweed season. The preseason and postseason biopsy specimens were taken 24 hours after ragweed allergen challenge and compared with the initial unchallenged biopsy specimen to assess cytokine and inflammatory cell responses by using immunocytochemistry and in situ hybridization. RESULTS: AIC was safe and well tolerated by all patients. There was no difference between the AIC and placebo groups in the number of allergen-induced major basic protein-, IL-4-, IL-5-, or IFN-gamma-positive cells in the mucosa in the first weeks after AIC immunization. On rechallenge and rebiopsy after the end of the 2001 ragweed season, however, AIC-treated patients had a significantly reduced increase in eosinophils and IL-4 mRNA-positive cells and an increased number of IFN-gamma mRNA-positive cells compared with placebo-treated patients. No difference between treatment groups was observed in symptom scores or medication use during the first ragweed season. During the second ragweed season, however, there was a significant decrease in chest symptoms and a trend toward reduced nasal symptoms in the AIC-treated group. CONCLUSION: Short-course immunotherapy with AIC can modify the response of nasal mucosa to allergen challenge by increasing T(H)1 cytokine production and decreasing T(H)2 cytokine production and eosinophilia. This modification was not immediate but was observed 4 to 5 months after completion of immunotherapy and seasonal ragweed-pollen exposure. The T-cell subset shift after immunization and seasonal exposure was followed by evidence of clinical efficacy in the second ragweed season without additional AIC immunizations. 相似文献
7.
Deleterious effects of minocycline in animal models of Parkinson's disease and Huntington's disease 总被引:6,自引:0,他引:6
Diguet E Fernagut PO Wei X Du Y Rouland R Gross C Bezard E Tison F 《The European journal of neuroscience》2004,19(12):3266-3276
Minocycline has been shown to exert anti-inflammatory effects underlying its putative neuroprotective properties in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease and in the R6/2 mouse model of Huntington's disease (HD). However, contradictory results have recently been reported. We report deleterious effects of minocycline in two phenotypic (toxic) models of Parkinson's disease and HD in monkey and mouse. Of seven MPTP-intoxicated female cynomolgus monkeys (0.2 mg/kg, i.v. until day 15), three received minocycline (200 mg b.i.d.). While placebo-MPTP-treated animals displayed mild parkinsonism at day 15, the minocycline/MPTP-treated animals tended to be more affected (P = 0.057) and showed a greater loss of putaminal dopaminergic nerve endings (P < 0.0001). In the 3-nitropropionic acid (3-NP) mouse model of HD, minocycline (45 mg/kg i.p.) was administered 30 min before each i.p. injection of 3-NP (b.i.d., cumulated dose, 360 mg/kg in 5 days). Mice receiving minocycline exhibited a worsening of the mean motor score with a slower recovery slope, more impaired general activity and significantly deteriorated performances on the rotarod, pole test and beam-traversing tasks. The histopathological outcome demonstrated that minocycline-treated mice presented significantly more severe neuronal cell loss in the dorsal striatum. The effect of minocycline vs. 3-NP was also investigated on hippocampal and cortical cell cultures. minocycline blocked 3-NP-induced neurotoxicity at certain doses (1 mm cortical neurons) but not at higher doses (10 mm). Thus, minocycline may have variable and even deleterious effects in different species and models according to the mode of administration and dose. 相似文献
8.
Behavioral and immunohistochemical effects of chronic intravenous and subcutaneous infusions of varying doses of rotenone 总被引:12,自引:0,他引:12
Fleming SM Zhu C Fernagut PO Mehta A DiCarlo CD Seaman RL Chesselet MF 《Experimental neurology》2004,187(2):418-429
Mitochondrial toxins such as the complex 1 inhibitor rotenone are widely used as pesticides and may be present in military environments. Administration of rotenone can induce biochemical and histological alterations similar to those of Parkinson's disease in rats. However, only a subset of animals show these effects and it is unclear whether more subtle alterations are caused by chronic administration of rotenone in those animals that appear resistant to its toxic effects on dopaminergic nerve terminals. To address this question, vehicle or rotenone (2.0, 2.5, or 3.5 mg/kg/day) was administered intravenously or subcutaneously for 21 days to adult rats, and rotenone effects on survival, motor behavior, and striatal tyrosine hydroxylase immunoreactivity (TH-IR) were examined. Both intravenous and subcutaneous rotenone induced a dose-dependent decrease in survival rates. Surviving animals showed a decrease in spontaneous rearing. Locomotor activity and movement initiation time were also altered in some of the experimental groups. Confirming previous results, TH-IR in the striatum was markedly decreased in rats that fell ill early in the study and in a few of the surviving rats with high rotenone doses. However, none of the surviving rats receiving 2.0 mg/kg/day showed TH-IR loss reminiscent of Parkinson's disease, and loss of striatal TH-IR across doses was not correlated with motor behavior in individual rats. Thus, chronic administration of low doses of rotenone induces motor anomalies even in animals that do not develop histological signs of Parkinson's disease, indicating a pervasive neurological effect of moderate mitochondrial dysfunction in vivo. 相似文献
9.
Lazor-Blanchet C Rusca S Vernez D Berry R Albrecht E Droz PO Boillat MA 《International archives of occupational and environmental health》2004,77(4):244-248
Background Waterproofing agents are widely applied to leather and textile garments; they are also used as floor stain protectors by professionals. Acute respiratory injury is described in three cases of young healthy adults following occupational inhalation of a new waterproofing formulation containing an acrylate fluoropolymer. Within 1 or 2 h after exposure they developed a rapidly progressive dyspnoea; two of them had hypoxaemia and flu-like reactions. All patients improved with supportive treatment in a few days. The mechanism of toxicity is still under investigation, but experimental data suggest the role of this new acrylate fluoropolymer.Conclusion Tilers should be warned against spraying floor stain repellents; there is also a need to make consumers aware that the spraying of waterproofing agents in a closed environment and concomitant smoking should be avoided. 相似文献
10.