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61.
Forissier JF Bonne G Bouchier C Duboscq-Bidot L Richard P Wisnewski C Briault S Moraine C Dubourg O Schwartz K Komajda M 《European journal of heart failure》2003,5(6):821-825
BACKGROUND: Mutations in LMNA gene encoding two ubiquitously expressed nuclear proteins, lamins A and C, give rise to up to 7 different pathologies affecting specific tissues. Three of these disorders affect cardiac and/or skeletal muscles with atrio-ventricular conduction disturbances, dilated cardiomyopathy and sudden cardiac death as common features. RESULTS: A new LMNA mutation (1621C>T, R541C) was found in two members of a French family with a history of ventricular rhythm disturbances and an uncommon form of systolic left ventricle dysfunction. The two patients: the proband and his daughter, were affected and exhibited an atypical form of dilated cardiomyopathy with an unexplained left ventricle aneurysm revealed by ventricular rhythm disturbances without atrio-ventricular block. CONCLUSION: This finding reinforces the highly variable phenotypic expression of LMNA mutation and emphasizes the fact that LMNA mutations can be associated with different cardiac phenotypes. 相似文献
62.
Dou L Cerini C Brunet P Guilianelli C Moal V Grau G De Smet R Vanholder R Sampol J Berland Y 《Kidney international》2002,62(6):1999-2009
BACKGROUND: Infectious diseases are among the most morbid events in uremia. The uremic toxin p-cresol may play a role in the immunodeficiency of uremia by depressing phagocyte functional capacity. Leukocyte adhesion to endothelium, a key event in the immune response, is mediated by endothelial adhesion molecules. These include intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, which are induced by various inflammatory cytokines. We asked whether p-cresol alters endothelial adhesion molecule expression and modifies endothelial/leukocyte adhesion. METHODS: Human umbilical vein endothelial cells (HUVEC) were incubated with p-cresol in the presence or absence of tumor necrosis factor (TNF) or interleukin-1beta (IL-1beta). Thereafter, the endothelial molecules ICAM-1, VCAM-1, and E-selectin were quantitated and the monocyte (THP-1) adhesion to HUVEC measured. RESULTS: P-cresol decreased cytokine-induced protein and mRNA expression of ICAM-1 and VCAM-1. In addition, p-cresol significantly decreased the adhesion of THP-1 to cytokine-stimulated HUVEC. CONCLUSIONS: P-cresol may play a role in the immune defect of uremic patients by inhibiting cytokine-induced endothelial adhesion molecule expression and endothelium/monocyte adhesion. 相似文献
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64.
Growth phase-dependent expression of ICAD-L/DFF45 modulates the pattern of apoptosis in human colonic cancer cells 总被引:10,自引:0,他引:10
Charrier L Jarry A Toquet C Bou-Hanna C Chedorge M Denis M Vallette G Laboisse CL 《Cancer research》2002,62(7):2169-2174
The inhibitor of caspase-3-activated DNase (ICAD) is a caspase-3 substrate that controls nuclear apoptosis. ICAD has two isoforms: a functional isoform of M(r) 45,000, ICAD-L/DNA fragmentation factor (DFF) 45; and a M(r) 35,000 isoform, ICAD-S/DFF35. ICAD-deficient murine cells display resistance to apoptotic stimuli and absence of typical nuclear changes of apoptosis. Our aim was to: (a) characterize the ICAD expression in several human colonic cancer cell lines compared with human normal colonocytes; and (b) correlate the phenotypic features of apoptosis to the level of ICAD expression. ICAD expression was assessed by immunoblot analysis. Early markers of apoptosis of cultured cells included lactate dehydrogenase retention in dying cells, cytokeratin 18 cleavage, and caspase-3 activation. Nuclear markers of apoptosis were assessed by Hoechst staining of nuclei, electron microscopy, and DNA electrophoresis. Inhibition of caspases was performed using a broad-spectrum caspase inhibitor, z-Val-Ala-Asp-fluoromethyl ketone. ICAD expression was restricted to the functional ICAD-L/DFF45 isoform in colonic cancer cells as well as in human normal colonocytes. In a clonal derivative of HT29 cells (HT29-Cl.16E cells), ICAD expression was found to be down-regulated during the exponential phase of growth, and the cell death triggered by IFN-gamma, anti-Fas antibody plus Adriamycin was characterized by the expression of early markers of apoptosis, whereas the key nuclear features of apoptosis were absent. In contrast, exposure of confluent cells to this treatment led to a typical apoptotic nuclear fragmentation. Both forms of apoptosis, in exponentially growing and confluent cells, were sensitive to the broad spectrum inhibitor of caspases, z-Val-Ala-Asp-fluoromethyl ketone. Our findings support the concept that the expression of ICAD is essential to the execution of full-blown apoptosis in colonic cancer cells. Altogether, our results point to ICAD as a potential target for restoring a normal apoptotic signal transduction pathway in colonic cancer cells. 相似文献
65.
BARD1 induces apoptosis by catalysing phosphorylation of p53 by DNA-damage response kinase 总被引:2,自引:0,他引:2
Feki A Jefford CE Berardi P Wu JY Cartier L Krause KH Irminger-Finger I 《Oncogene》2005,24(23):3726-3736
The BRCA1-associated RING domain protein BARD1 acts with BRCA1 in double-strand break repair and ubiquitination. BARD1 plays a role as mediator of apoptosis by binding to and stabilizing p53, and BARD1-repressed cells are resistant to apoptosis. We therefore investigated the mechanism by which BARD1 induces p53 stability and apoptosis. The apoptotic activity of p53 is regulated by phosphorylation. We demonstrate that BARD1 binds to unphosphorylated and serine-15 phosphorylated forms of p53 in several cell types and that the region required for binding comprises the region sufficient for apoptosis induction. In addition, BARD1 binds to Ku-70, the regulatory subunit of DNA-PK, suggesting that the mechanism of p53-induced apoptosis requires BARD1 for the phosphorylation of p53. Upregulation of BARD1 alone is sufficient for stabilization of p53 and phosphorylation on serine-15, as shown in nonmalignant epithelial cells and ovarian cancer cells, NuTu-19, which are defective in apoptosis induction and express aberrant splice variants of BARD1. Stabilization and phosphorylation of p53 in NuTu-19 cells, as well as apoptosis, can be induced by the exogenous expression of wild-type BARD1, suggesting that BARD1, by binding to the kinase and its substrate, catalyses p53 phosphorylation. 相似文献
66.
Solassol I Bressolle F Caumette L Garcia F Poujol S Culine S Pinguet F 《Therapeutic drug monitoring》2005,27(4):491-498
Perception of pain by the patient is frequently one of the early signs preceding a diagnosis of cancer and, later, a sinister sign of disease progression. Among opioid drugs, transdermal fentanyl has been evaluated in the treatment of moderate to severe cancer pain. The objective of this study was to investigate the intra- and interindividual variabilities in pharmacokinetics after fentanyl drug delivery by the transdermal fentanyl patch delivery system in patients with cancer pain. As a first step, a liquid chromatography-mass spectrometry method was developed for the determination of the analgesic fentanyl in human plasma. This method was validated over the concentration range 0.15-100 ng/mL. The study group consisted of 29 inpatients (18 men and 11 women; age range 29-80 years). The initial transdermal fentanyl delivery rate was chosen depending on the patient's analgesic requirements. For 20 patients, the initial TTS fentanyl delivery rate was 25 or 50 microg/h. For 6 patients, the initial delivery rate was 75-150 microg/h. Two patients received up to 300 microg/h fentanyl delivery rate, and 3 patients received up to 350 microg/h fentanyl delivery rate. Fifteen of the 29 patients received rescue doses of subcutaneous or oral morphine, and 26 patients received paracetamol with codeine (30 mg per os). Blood samples were collected at the following intervals: 2-5, 22-26, or 45-47 hours following fentanyl patch application. The severity of pain experienced by the patient was assessed thrice daily using a visual analogue scale. The study period was 46 days. Large patient-to-patient variations in pharmacokinetic parameters occurred, although intraindividual variability was limited. A mean bioavailability of 78% was estimated; the total clearance averaged 41 L/h. From 25 to 100 mug/h fentanyl delivery rate, the pharmacokinetics was linear. At the 2 highest doses, an increase of total clearance was observed (>60 L/h). For the whole group, transdermal fentanyl treatment provided good to excellent pain relief in the majority of patients. 相似文献
67.
Berthelot JM Tortellier L Guillot P Prost A Caumon JP Glemarec J Maugars Y;SRO 《Joint, bone, spine : revue du rhumatisme》2005,72(1):66-68
OBJECTIVES: To assess the frequency, features, and outcome of excruciating lumbar, dorsal, and/or thoracic pain following injections of local corticosteroids in rare instances. METHODS: A questionnaire mailed to 500 French rheumatologists. RESULTS: Three hundred and eighteen cases were reported by 92 rheumatologists (one event per 8000 injections or 6.5 years of practice), following injections into lumbar epidural space (39%), an upper limb (30%), a lower limb (mostly the heel) (24%), or other locations (7%), of cortivazol (67%), hydrocortisone (25%), betamethasone (7%), or paramethasone (1%). Symptoms occurred 1-5 min (78%) or less than 1 min (22%) after injection, and highly acute axial pain usually lasted for less than 5 min (34%) or 5-15 min (51%). In addition to pain in lumbar (84%) and/or dorsal regions (25%) [often preceded or associated with thoracic pain (36%)], other signs were: anxiety (87%), shortness of breath (64%), facial flushing (64%), diffuse sweating (41%), agitation (29%), transient cough (23%), abdominal pain (20%), transient hypertension (15%), paleness (10%), hypotension (8%), diarrhoea (3%) and headache (3%). None of these patients was known to be allergic, and urticaria developed in only 2%. Outcome was favourable in all cases (even though 4/318 patients were transiently hospitalised) with an overall duration of 25 +/- 71 min. Another injection was performed later in 146/318 cases (46%), but Tachon's syndrome recurred in only 20 of these 146 patients (14%). CONCLUSION: The outcome of this impressive syndrome seems excellent. Tachon's syndrome might be the venous counterpart of Nicolau's syndrome (injection of corticosteroids in an artery). 相似文献
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70.
Labauge P Fogli A Castelnovo G Le Bayon A Horzinski L Nicoli F Cozzone P Pagès M Briere C Marty-Double C Delhaume O Gelot A Boespflug-Tanguy O Rodriguez D 《Annals of neurology》2005,58(4):634-639
Leukoencephalopathy with vanishing white matter syndrome (childhood ataxia with central nervous system hypomyelination/vanishing white matter disease) is an autosomal recessive disorder characterized by the occurrence of acute episodes of deterioration after minor head trauma or infection, and symmetrical demyelination on magnetic resonance with cavitation aspects. Mutations in each of the five subunits of eIF2B have been identified. We report in an affected man and his mother an adult-onset form of childhood ataxia with central nervous system hypomyelination/vanishing white matter disease-like disorder with no mutations in the EIF2B genes and normal guanine nucleotide exchange factor eIF2B activity, suggesting a new dominant inheritance of this syndrome that may involve other genes. 相似文献