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71.
The Effects of Permeation Enhancers on the Surface Morphology of the Rat Nasal Mucosa: A Scanning Electron Microscopy Study 总被引:2,自引:0,他引:2
A rat model has been developed to compare relative morphological changes in the nasal mucosa after exposure to potential membrane permeation enhancers. Scanning electron microscopy was used to characterize gross structural and specific cellular changes following exposure. Micrographs of the rat nasal mucosa were scored in four categories: (1) mucosal surface integrity, (2) ciliary morphology, (3) mucus/extracellular debris, and (4) presence of red blood cells. The order of increasing morphological damage resulting from a 5-min exposure to each surfactant was 0.5% Solulan C-24 0.5% Solulan C-24/0.5% sodium tauro-24,25-dihydrofusidate (STDHF) < 0.5% STDHF < 1.0% STDHF 1.0% Laureth-9 < 1.0% sodium taurodeoxycholate 1.0% sodium deoxycholate. The changes observed in the mucosal morphology after exposure to the various surfactants are in general agreement with data in the literature. This model is able to compare rapidly the relative morphological effects on the mucosal membrane of different nasal formulations. 相似文献
72.
Katharine Edgerley Lisa Bryson Lucy Hanington Rachel Irving Shelagh Joss Anne Lampe Isabelle Maystadt Deborah Osio Ruth Richardson Miranda Split Francis H. Sansbury Ingrid Scurr Helen Stewart Alisdair McNeil Karen Low 《American journal of medical genetics. Part A》2023,191(5):1447-1458
To delineate further the clinical phenotype of Lamb–Shaffer Syndrome (LSS) 16 unpublished patients with heterozygous variation in SOX5 were identified either through the UK Decipher database or the study team was contacted by clinicians directly. Clinical phenotyping tables were completed for each patient by their responsible clinical geneticist. Photos and clinical features were compared to assess key phenotypes and genotype–phenotype correlation. We report 16 SOX5 variants all of which meet American College of Medical Genetics/Association for Clinical Genomic Science ACMG/ACGS criteria class IV or V. 7/16 have intragenic deletions of SOX5 and 9/16 have single nucleotide variants (including both truncating and missense variants). The cohort includes two sets of monozygotic twins and parental gonadal mosaicism is noted in one family. This cohort of 16 patients is compared with the 71 previously reported cases and corroborates previous phenotypic findings. As expected, the most common findings include global developmental delay with prominent speech delay, mild to moderate intellectual disability, behavioral abnormalities and sometimes subtle characteristic facial features. We expand in more detail on the behavioral phenotype and observe that there is a greater tendency toward lower growth parameters and microcephaly in patients with single nucleotide variants. This cohort provides further evidence of gonadal mosaicism in SOX5 variants; this should be considered when providing genetic counseling for couples with one affected child and an apparently de novo variant. 相似文献
73.
Harry T. Whelan Lucy H. Kras Kutlan Ozker Dawn Bajic Meic H. Schmidt Yu Liu Lisa Ann Trembath Fusun Uzum Glenn A. Meyer Annette D. Segura B. David Collier 《Journal of neuro-oncology》1994,22(1):7-13
The use of PHOTOFRIN for photodynamic therapy of human gliomas has been studied by i.v. administration and laser photosensitization. Defining the uptake of PHOTOFRIN in the patient's tumor in comparison with the surrounding normal brain tissue is highly desirable for patient selection and study ofin vivo kinetics. We utilized a non-invasive approach to the detection of PHOTOFRIN uptake in brain tumors with111In-oxine radiolabeled PHOTOFRIN and external imaging and quantitation using a gamma camera. Biodistribution of111In-labeled PHOTOFRIN in 13 organs was determined in four dogs and 15 mice with gliomas.99mTc-DTPA was used as a control for nonspecific uptake. The greatest concentration of111In-PHOTOFRIN in the brain tumor occurred at 24 hours post i.v. administration. The brain tumor PHOTOFRIN uptake was seven times greater than that of normal brain. The decreased blood background at 72 hours made this the optimum time for imaging. Specific tumor tissue uptake of111In-PHOTOFRIN occurred, well beyond that resulting from blood-brain-barrier (BBB) breakdown. 相似文献
74.
Disposition in mice of 7-hydroxystaurosporine,a protein kinase inhibitor with antitumor activity 总被引:1,自引:0,他引:1
Donald L. Hill Kathleen F. Tillery Lucy M. Rose Claude F. Posey 《Cancer chemotherapy and pharmacology》1994,35(1):89-92
UCN-01, a hydroxylated derivative of staurosporine, was selected for study because of its promising antitumor activity. For mice dosed intravenously, subcutaneously, or by oral gavage with this compound, the maximum tolerated doses (MTD) were 20, 10, and >100 mg/kg, respectively. UCN-01 was stable in mouse and dog plasma, but in human plasma it was converted to a metabolite in a process not inhibited by standard protease and esterase inhibitors. Following n intravenous dose of 10 mg/kg UCN-01, the half-lives for the initial (t
1/2) and terminal (t
1/2) exponential phases of elimination were 10 and 85 min, respectively; the area under the plasma concentration-time curve (AUC value) was 117 g min ml–1. In mice dosed by oral gavage with 10 mg/kg, the calculated value for the half-life of the elimination phase was 150 min. The AUC value was 15 g min ml–1, giving a value for bioavailability of 13%. After subcutaneous dosing with 10 mg/kg, the calculated values for half-lives for the distribution and elimination phases were 23 and 130 min, respectively; the AUC value was 113 g min ml–1. Since this value is equivalent to that obtained for intravenous dosing, administration of UCN-01 by the subcutaneous route may be an alternative to intravenous dosing in preclinical and clinical trials.This work was supported by contract NO1-CM-27710 (National Cancer Institute, National Institutes of Health, Department of Health and Human Services) 相似文献
75.
Makaula NA Marasas WF Badenhorst CJ Bradshaw D Swanevelder S 《African journal of health sciences》1995,2(3):333-337
New data regarding the incidence of oesophageal and other cancers during the period 1985-1990 are reported for all clinics and hospitals in four selected districts of Transkei, Southern Africa i.e Kentani, Butterworth, Lusikisiki and Bizana. Active and passive methods were used to obtain the hospital-based cancer registry data. The mean annual number of cancer cases recorded for the period 1985-1990 was 292. Age-standardized incidence rates (ASIIR, African Standard) for all recorded cancers were 81.4 and 52.6/100,000 for males and females, respectively. Histopathogical examination of 52.6% of recorded tumours revealed that 67.3% were squamous carcinomas, 21.7% adenocarcinomas and the remainder non-epithelial neoplasms. Cancer of the oesophagus (EC) was the most frequently recorded cancer and accounted for 46.5% of the cases with mean ASIR of 46.7 and 19.2/100,000 for males and females, respectively. The male/female ratio was 2:4:1. The highest mean ASIR per annum for OC in males (55.6/100,000) occurred in Kentani and in females (22.3/100,000) in Lusikisiki, whereas the lowest rates in both sexes (37.0 and 11.7/100,000 respectively) occurred in Bizana. Comparison of the OC rates in the four districts of Transkei during 1985-1990 with previously reported trends, confirms a consistently high rate in the south-western district of Kentani during the past 35 years and progressively increasing rates in the north-eastern districts of Bizana and Lusikisiki. These results have profound implications for further epidemiological and aetiological studies on OC in Transkei, but need to be corroborated by data from other sources such as statistics on histologically diagnosed cancer in Transkei by district in the South African National Cancer Registry. The second most frequently recorded cancer among males was liver cancer with a mean annual ASIR of 6.0/100,0000 and a male: female ratio of 3:1. The most frequently recorded cancer with a mean annual AISR of 20.9/100,000 followed by OC (19.2/100,000) and breast cancer (5.8/100,000). 相似文献
76.
77.
78.
79.
Neil E Martin Thomas B Brunner Krystina D Kiel Thomas F DeLaney William F Regine Mohammed Mohiuddin Ernest F Rosato Daniel G Haller James P Stevenson Debbie Smith Barnali Pramanik Joel Tepper Wesley K Tanaka Briggs Morrison Paul Deutsch Anjali K Gupta Ruth J Muschel W Gillies McKenna Eric J Bernhard Stephen M Hahn 《Clinical cancer research》2004,10(16):5447-5454
PURPOSE: Preclinical and clinical studies have demonstrated that inhibition of prenylation can radiosensitize cell lines with activation of Ras and produce clinical response in patients with cancer. The aim of this study was to determine the maximally tolerated dose of the dual farnesyltransferase and geranylgeranyltransferase I inhibitor L-778,123 in combination with radiotherapy for patients with locally advanced pancreatic cancer. EXPERIMENTAL DESIGN: L-778,123 was given by continuous intravenous infusion with concomitant radiotherapy to 59.4 Gy in standard fractions. Two L-778,123 dose levels were tested: 280 mg/m2/day over weeks 1, 2, 4, and 5 for dose level 1; and 560 mg/m2/day over weeks 1, 2, 4, 5, and 7 for dose level 2. RESULTS: There were no dose-limiting toxicities observed in the eight patients treated on dose level 1. Two of the four patients on dose level 2 experienced dose-limiting toxicities consisting of grade 3 diarrhea in one case and grade 3 gastrointestinal hemorrhage associated with grade 3 thrombocytopenia and neutropenia in the other case. Other common toxicities were mild neutropenia, dehydration, hyperglycemia, and nausea/vomiting. One patient on dose level 1 showed a partial response of 6 months in duration. Both reversible inhibition of HDJ2 farnesylation and radiosensitization of a study patient-derived cell line were demonstrated in the presence of L-778,123. K-RAS mutations were found in three of the four patients evaluated. CONCLUSIONS: The combination of L-778,123 and radiotherapy at dose level 1 showed acceptable toxicity in patients with locally advanced pancreatic cancer. Radiosensitization of a patient-derived pancreatic cancer cell line was observed. 相似文献
80.
Taurine is an abundant amino acid found in mammalian tissues and it has been suggested to have cyto-protective functions. The aim of the present study was to determine if taurine had the potential to reduce oxidative stress associated with metal-stimulated catecholamine oxidation. Taurine and structural analogs of taurine were tested for their ability to inhibit metal-stimulated quinone formation from dopamine or L-dopa. Oxidative damage to proteins and lipids were also assessedin vitro and the effects of taurine were determined. Taurine (20 mM) was found to decrease significantly ferric iron (50–500 μM)- and manganese (10 μM)-stimulated L-dopa or dopamine oxidation. Taurine had no effect on zinc-induced dopamine oxidation and slightly potentiated copper- and NaIO4-stimulated quinone formation. Ferric iron-stimulated lipid peroxidation was not affected by taurine (1–20 mM). Protein carbonyl formation induced by ferric iron (500 μM) and L-dopa (500 μM) was significantly reduced by 10 mM taurine. The cytotoxicity of L-dopa (250 μM) and ferric chloride (75 μM) to LLC-PK1 cells was attenuated by 10 mM taurine or hypotaurine. Homotaurine alone stimulated L-dopa oxidation and potentiated the cytotoxic effects of ferric iron. Homotaurine was found to be cytotoxic when combined with L-dopa or L-dopa/iron. In contrast, hypotaurine inhibited quinone formation and protected LLC-PK1 cells. These studies suggest that taurine may exhibit cytoprotective effects against the oxidation products of catecholamines by acting as a scavenger for free radicals and cytotoxic quinones. 相似文献