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Knežević AH Dikić D Lisičić D Kopjar N Oršolić N Karabeg S Benković V 《Basic & clinical pharmacology & toxicology》2011,109(5):343-349
Swiss albino mice were given Ehrlich ascites tumour cells (1 × 10(6)) intraperitoneally. For survival analysis and tumour growth analysis, the mice were administered quercetin and naringin (100 mg/kg) daily for 3 consecutive days, beginning on the third day after intraperitoneal (i.p.) injection of Ehrlich ascites tumour cells (1 × 10(6)). Irinotecan was administered ip at a dose of 50 mg/kg on days 1, 13 and 19. For the analysis of cell types and differential count of cells present in the peritoneal cavity, peripheral whole-blood leucocyte count and the comet assay, the mice were treated therapeutically with quercetin and naringin (100 mg/kg) and irinotecan (50 mg/kg) daily for 3 consecutive days beginning on third day after i.p. injection of Ehrlich ascites tumour cells (1 × 10(6)). We observed the synergistic anti-tumour effect expressed as the median survival time of mice treated with naringin in combination with irinotecan. All test components inhibited tumour growth and increased lifespan of mice except quercetin. The total number of cells present in the peritoneal cavity of mice significantly decreased in all treatments except quercetin. Single irinotecan and irinotecan combined with naringin had the highest DNA-damaging potential on peripheral blood leucocytes and lowest primary DNA damage, both in the kidney and liver cells as measured by the alkaline comet assay. Our results showed enhanced anti-tumour activity of irinotecan in combined treatment with flavonoids to reduce the deteriorating reaction of cytostatic drugs. 相似文献
54.
Ivančica Ternjej Zlatko Mihaljević Igor Stanković Mladen Kerovec Laszlo Sipos Davor Želježić Nevenka Kopjar 《Archives of environmental contamination and toxicology》2010,59(2):182-193
To estimate the impacts of an Al-contaminated aquatic environment on DNA integrity in the blood cells of eastern mosquitofish
Gambusia holbrooki Girard 1859 inhabiting Lake Njivice (Island of Krk, Croatia), an evaluation using the alkaline comet assay was carried out.
Genome integrity was studied in parallel with the same fish species inhabiting the nearby, unpolluted Lake Ponikve. The amount
of DNA damage in cells was estimated from three different parameters: comet tail length as the extent of genetic material
migration, tail intensity (% DNA in the comet tail) and tail moment. The results indicate the loss of genome integrity in
blood cells of mosquitofish inhabiting Lake Njivice and the genotoxicity of this aquatic environment. Using the same assay,
acute genotoxicity of contaminated water and sediment was evaluated and confirmed on fish, mouse and human blood cells treated
ex vivo. Results of the present study indicate that the alkaline comet assay applied to fish blood cells is a valuable tool
for determining the potential genotoxicity of water pollutants and confirm its usefulness in the evaluation of DNA damage
in fish living in Al-polluted waters. 相似文献
55.
Das R Dimitrova N Xuan Z Rollins RA Haghighi F Edwards JR Ju J Bestor TH Zhang MQ 《Proceedings of the National Academy of Sciences of the United States of America》2006,103(28):10713-10716
Epigenetic effects in mammals depend largely on heritable genomic methylation patterns. We describe a computational pattern recognition method that is used to predict the methylation landscape of human brain DNA. This method can be applied both to CpG islands and to non-CpG island regions. It computes the methylation propensity for an 800-bp region centered on a CpG dinucleotide based on specific sequence features within the region. We tested several classifiers for classification performance, including K means clustering, linear discriminant analysis, logistic regression, and support vector machine. The best performing classifier used the support vector machine approach. Our program (called hdfinder) presently has a prediction accuracy of 86%, as validated with CpG regions for which methylation status has been experimentally determined. Using hdfinder, we have depicted the entire genomic methylation patterns for all 22 human autosomes. 相似文献
56.
The proper intensity and illumination time of a curing light is of great importance for the complete polymerization of resin composites and long-lasting resin composite restorations. Inadequately cured resin composites can have a cytotoxic effect on pulp tissue by releasing unreacted monomers. This study determined whether there is any difference in cytotoxicity between composite materials illuminated with different curing modes of LED curing units. Thin layers of two composite materials were polymerized using three different modes of the Bluephase C8 LED curing unit: a high intensity mode (HIP-800 mW/cm2, 20 seconds), a soft-start mode (SOF-650 mW/cm2 first 5 seconds, 800 mW/cm2 next 25 seconds) and a low intensity mode (LOP-650 mW/cm2, 30 seconds). Lymphocyte cultures were treated with both polymerized and unpolymerized composites using one of the modes stated above. Cells were analyzed using the trypan blue exclusion test, the acridine orange/ethidium bromide dying technique and an alkaline comet assay. Significant cytotoxicity was observed for 120 mg of unpolymerized composites and those polymerized with the HIP polymerization mode. A significant level of DNA damage was detected for 120 mg of unpolymerized composites. However, curing via the LOP program exhibited the lowest genotoxicity. Longer curing time with lower intensity results in less cytotoxicity than shorter curing exposure using a higher intensity of light emitted from the curing light source. 相似文献
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Štefan Blazina Gašper Markelj Anja Koren Jeverica Nataša Toplak Nevenka Bratanič Janez Jazbec Peter Kopač Maruša Debeljak Alojz Ihan Tadej Avčin 《Journal of clinical immunology》2016,36(8):764-773
An abnormal regulation of immune responses leads to autoimmune and inflammatory manifestations in patients with primary immunodeficiencies (PIDs). The objective of our study was to evaluate the frequency of non-infectious and non-malignant manifestations in a large cohort of patients included in the Slovenian national PID registry and to assess the time of manifestation onset with respect to the time of PID diagnosis. Medical records of registered patients were reviewed. Data on autoimmunity, lymphoproliferation, autoinflammation, allergies, PID diagnosis, and underlying genetic defects were collected and analyzed. The time of each manifestation onset was determined and compared with the time of PID diagnosis. As of May 2015, 247 patients with 50 different PIDs were registered in the Slovenian national PID registry (147 males, 100 females; mean age 20 years). Mean disease duration was 14 years; 78 % of patients were younger than 18 years; and 22 % of patients were adults. Diagnosis of PID was genetically confirmed in 51 % of patients. Non-infectious and non-malignant manifestations were present in 69/235 (29 %) patients, including autoimmune manifestations in 52/235 (22 %), lymphoproliferative/granulomatous in 28/235 (12 %), autoinflammatory in 12/247 (5 %), and allergic manifestations in 10/235 (4 %) of all registered patients. Autoimmune manifestations were present in all patients whose PIDs were classified as diseases of immune dysregulation, 47 % of patients with chronic granulomatous disease, and 38 % of patients with predominantly antibody immune deficiencies. A high prevalence of non-infectious and non-malignant manifestations among patients in the Slovenian national PID registry suggests common genetic factors of autoimmunity, inflammation, and immunodeficiency. Patients with PID should be routinely screened for autoimmune and inflammatory manifestations at the time of PID diagnosis and during the long-term follow up. 相似文献
59.
Vesna Benkovic Anica Horvat Knezevic Nada Orsolic Ivan Basic Snjezana Ramic Tomislav Viculin Fabijan Knezevic Nevenka Kopjar 《Phytotherapy research : PTR》2009,23(8):1159-1168
This in vitro study aimed to evaluate the possible radioprotective effects of the natural substances WSDP, caffeic acid, chrysin and naringin on γ‐irradiated human white blood cells. The effectiveness of tested compounds was evaluated using the alkaline comet assay, the analysis of structural chromosome aberration and the cytokinesis‐block micronucleus assay. The results obtained by the alkaline comet study indicate favourable toxicity profiles of propolis and its polyphenolic components, and confirmed the radioprotective abilities comparable to the chemical radioprotector AET. WSDP and its polyphenolic components were able to reduce the number of necrotic cells. None of tested compounds induced significant genotoxicity, but all of them offered a quite measurable protection against DNA damage. WSDP was found to be the most effective in diminishing the levels of primary and more complex cytogenetic DNA damage in white blood cells. Considering its complex composition, to undoubtedly explain the underlying mechanisms of cyto/radioprotective effects, further studies are needed. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
60.
Normal human blood received in 0.02 M sodium oxalate (1 part to 9 parts of blood) in 16 × 100 mm glass tubes, at 37 °C, always clotted. Blood from severe Factor X deficiency received in 0.02 M sodium oxalate did not clot. The prothrombin time of the 0.02 M oxalate Stuart plasma was much shorter than the prothrombin time of the 0.1 M oxalate Stuart plasma. The prothrombin time of the 0.1 M oxalate Stuart plasma was shorter with 0.02 M than with 0.01 M CaCl2. The Stypven Time of this 0.1 M oxalate plasma was very prolonged but was almost normal with the 0.02 M oxalate plasma. Almost normal prothrombin time (with human brain thromboplastin) of a ten times concentrated 0.02 M oxalate Stuart plasma was observed. With 0.01 ml of a 1 % 0.02 M oxalate Stuart plasma for 0.1 ml of Factor VII deficient plasma the prothrombin time became normal. Same experiment with 0.1 M oxalate Stuart plasma did not normalize the prothrombin time.
Very abnormal kaolin partial thromboplastin time for the 0.1 M oxalate Stuart plasma and completely normal for the 0.02 M oxalate Stuart plasma was observed. We can postulate that the activation of the contact factors (F-XII, F-XI) occurs with traces of calcium ions not removed by the anticoagulant. Consequently, a condition can be generated which makes more manifest the limited amounts of normal F-X molecules in the deficient plasma. 相似文献