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41.
Reactivity of 9‐aminoacridine drug quinacrine with glutathione limits its antiprion activity 下载免费PDF全文
Martin Šafařík Tibor Moško Zbigniew Zawada Eva Šafaříková Martin Dračínský Karel Holada Jaroslav Šebestík 《Chemical biology & drug design》2017,89(6):932-942
Quinacrine—the drug based on 9‐aminoacridine—failed in clinical trials for prion diseases, whereas it was active in in vitro studies. We hypothesize that aromatic nucleophilic substitution at C9 could be contributing factor responsible for this failure because of the transfer of acridine moiety from quinacrine to abundant glutathione. Here, we described the semi‐large‐scale synthesis of the acridinylated glutathione and the consequences of its formation on biological and biophysical activities. The acridinylated glutathione is one order of magnitude weaker prion protein binder than the parent quinacrine. Moreover, according to log DpH 7.4, the glutathione conjugate is two orders of magnitude more hydrophilic than quinacrine. Its higher hydrophilicity and higher dsDNA binding potency will significantly decrease its bioavailability in membrane‐like environment. The glutathione deactivates quinacrine not only directly but also decreases its bioavailability. Furthermore, the conjugate can spontaneously decompose to practically insoluble acridone, which is precipitated out from the living systems. 相似文献
42.
Karmen Godič Torkar Mirjana Dražetić 《International journal of environmental health research》2017,27(4):293-305
The microbiological quality of bathing water and the surfaces of the surrounding pool platforms of two pools was estimated. ESBL- and MBL-producing Gram-negative bacteria isolated from water and surface samples were also studied. The water samples were satisfactory in 31 (86.1 %) out of 36 cases. Pseudomonas aeruginosa as well as Escherichia coli were identified in only 2 (5.5 %) cases. There were no correlations between the HPC and number of enterobacteria in the pool water and those found in the surface samples. Isolated strains were resistant to ticarcillin with clavulanic acid in 52.3 % of cases; all of them were susceptible to ciprofloxacin. The sequences for blaCTX-M were found in 21.6 % of strains, mostly from the groups blaCTX-M9 and blaCTX-M25, whilst the genes for chosen carbapenemases were noted in 15 (17.0 %) of strains. It is necessary to implement new approaches to monitoring resistant bacteria, not only clinical ones but also those found in other public environments. 相似文献
43.
The aim of this work was to study some morphological and morphometric parameters of leucocytes from blood smears of adult armadillosChaetophractus villosus (Mammalia, Dasypodidae). We also analysed the significance of the different sources of variation in these measurements. Blood samples were obtained through heart puncture, using plastic syringes without anticoagulant, in anaesthetised, wild, healthy animals (n=25). Two blood smears of each animal were stained with May Grünwald-Giemsa. Maximum and minimum diameters were measured for each type of leucocyte (n=10 for the most abundant ones: neutrophils and lymphocytes, andn=5 for others: eosinophils, basophils and monocytes). A hierarchical decomposition of the different sources of variation (animals, samples and cells) was carried out using pure model II nest ANOVA. This analysis was applied to both measured parameters. The variation components related to cells were always higher than those related to animals. Estimation of the selected parameters was only marginally changed between samples of the animal. The nuclei of both neutrophils and eosinophils were morphologically similar, generally with four or more lobes. The cytoplasm and neutrophils was only lightly stained. Lymphocytes are the smallest cell type, whereas basophils and lymphocytes are the roundest ones. Eosinophils and basophils are the cell types most variable in size. We suggest that for further studies the effort of sampling be aimed at measuring a larger number of cells from a moderate number of animals. Our results should represent the normal morphological and morphometrical characteristics of leucocytes of wild, healthy animals of this species. 相似文献
44.
Rectal cancer is one of the most common malignancies in the western world population. The management of rectal cancer has changed thoroughly in recent years owing to the rapid advances in surgical techniques, imaging and adjuvant therapy. The present study analyses extensively 152 patients operated for diagnosis of, rectal cancer in the First Clinic of General Surgery UHC "Mother Theresa" in Tirana, Albania, in a ten years period. In the medical and operative records were analysed demographic, diagnostic, clinic, operative, pathology and postoperative patient's data. M : F ratio was 1,5:1. The average age of all patients was 59,8 ± 12,2 (29 - 79) years. 48% of all patients were of the age group 61 - 70 years. The diagnosis interval was 6 ± 4,6 months. The mean distance of tumor from the anal verge was 8,3 ± 4,2 (3,7 - 16) cm. 30% of all patients resulted stage D, according to the Astler - Coller classification. Overall operability index was 97,5%. 30 % of patients were treated with palliative operative procedures. 67,5% of all patients were treated with curative intent. The most common curative operation was low anterior resection with mesorectal excision in 76 patients (51%). The mean postoperative hospital stay was 12 ± 9,7 (3 - 45) days. Overall postoperative morbidity and mortality were 30% and 2,6% respectively. The surgical treatment of rectal cancer has changed radically in recent years in Albania. Relatively new surgical techniques, like low anterior resection and use of adjuvant chemoradiotherapy have improved the outcome, quality of life and survival of our patients. 相似文献
45.
Ecotoxicological assessment of industrial effluent using duckweed (Lemna minor L.) as a test organism 总被引:1,自引:0,他引:1
Radić Sandra Stipaničev Draženka Cvjetko Petra Mikelić Ivanka Lovrenčić Rajčić Marija Marijanović Širac Siniša Pevalek-Kozlina Branka Pavlica Mirjana 《Ecotoxicology (London, England)》2010,19(1):216-222
This study aimed at assessing the toxic effects of industrial effluents using duckweed (Lemna minor L.) plants as a test system. Growth inhibition test according to standardized protocol (ISO 20079) was performed. The suitability
of the Comet assay (indicates DNA damage) and certain parameters such as peroxidase activity and lipid peroxidation level,
as biomarkers for environmental monitoring was evaluated. The water samples were collected monthly over a 3-month period from
the stream near the industrial estate of Savski Marof, Croatia. All samples caused inhibition of growth rates based on frond
number and biomass as well as decrease of chlorophylls content. In contrast, peroxidase activity, malondialdehyde content
and tail extent moment (measure of DNA strand breaks) markedly increased. Obtained data demonstrate the relevance of duckweed
as sensitive indicators of water quality as well as the significance of selected biological parameters in the reliable assessment
of phyto- and genotoxic potential of complex wastewaters. 相似文献
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48.
J Oral Pathol Med (2010) 39 : 257–262 Objective: The aim of this study was to qualitatively and semi‐quantitatively analyze mast cells in periapical lesions. Materials and methods: Biopsy specimens of 96 periapical lesions were stained with hematoxylin–eosin, histochemical Giemsa and immunohistochemical CD 117 (C kit) antibody. Mast cell count below 100 mast cells on 1000 fields of high power magnification was noted as ‘negative’, 101–400 as ‘mild’, 401–800 cells as ‘moderate’, and over 800 cells as ‘severe’. Results: Mast cells are found in 68 (70.8%) lesions. The presence of mast cells was greater in cysts than in granulomas (P < 0.0028). There was no difference in semi‐quantitative expression of CD 117 in granulomas and cysts (P > 0.05). Mast cells were placed in both: inflammatory infiltrate and in fibroblastic areas of periapical lesions, and their presence was most frequently mild to moderate. Conclusions: The findings of present study could suggest a role of mast cells in regulation of cellular immune mechanisms in periapical lesions, balancing between alterative and reparatory processes in inflamed periapical tissue. 相似文献
49.
Dra C. Moreno E. Ardanaz J. E. Olivera J. Castilla J. de Pedro-Cuesta 《European journal of epidemiology》1994,10(2):129-134
An apparent temporal-spatial cluster of Sudden Infant Death Syndrome (SIDS) was noted in the Autonomous Community of Navarre, Spain, when four unrelated children aged between 1 and 6 months died unexpectedly within a 7-day interval in January, 1990. The population under one year of age in Navarre was approximately 4,800. The scan test of temporal clustering showed that the sudden infant deaths occurred closer to one another in time significantly more often than would be expected by chance. All four infants lived in a neighbourhood of the capital of Navarre, which accounts for approximately half the region's population. The clustered cases coincided with an outbreak of influenza type A detected by the epidemiological surveillance system and seen by the increase in 1990 over the same period in the previous year in the number of paediatric emergency-ward admissions during the epidemic days. The results confirm the presence of a temporal-spatial cluster of SIDS and favour an environmental etiology where exposure to influenza A viruses is implicated. 相似文献
50.