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排序方式: 共有298条查询结果,搜索用时 15 毫秒
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Tagmose TM Schou SC Mogensen JP Nielsen FE Arkhammar PO Wahl P Hansen BS Worsaae A Boonen HC Antoine MH Lebrun P Hansen JB 《Journal of medicinal chemistry》2004,47(12):3202-3211
Phenylcyanoguanidines substituted with lipophilic electron-withdrawing functional groups, e.g. N-cyano-N'-[3,5-bis-(trifluoromethyl)phenyl]-N' '-(cyclopentyl)guanidine (10) and N-cyano-N'-(3,5-dichlorophenyl)-N' '-(3-methylbutyl)guanidine (12) were synthesized and investigated for their ability to inhibit insulin release from beta cells, to repolarize beta cell membrane potential, and to relax precontracted rat aorta rings. Structural modifications gave compounds, which selectively inhibit insulin release from betaTC6 cells (e.g. compound 10: IC(50) = 5.45 +/- 1.9 microM) and which repolarize betaTC3 beta cells (10: IC(50) = 4.7 +/- 0.5 microM) without relaxation of precontracted aorta rings (10: IC(50) > 300 microM). Inhibition of insulin release from rat islets was observed in the same concentration level as for betaTC6 cells (10: IC(50) = 1.24 +/- 0.1 microM, 12: IC(50) = 3.8 +/- 0.4 microM). Compound 10 (10 microM) inhibits calcium outflow and insulin release from perifused rat pancreatic islets. The mechanisms of action of 10 and 12 were further investigated. The compounds depolarize mitochondrial membrane from smooth muscle cells and beta cell and stimulate glucose utilization and mitochondrial respiration in isolated liver cells. Furthermore, 10 was studied in a patch clamp experiment and was found to activate Kir6.2/SUR1 and inhibit Kir6.2/SUR2B type of K(ATP) channels. These studies indicate that the observed effects of the compounds on beta cells result from activation of K(ATP) channels of the cell membrane in combination with a depolarization of mitochondrial membranes. It also highlights that small structural changes can dramatically shift the efficacy of the cyanoguanidine type of selective activators of Kir6.2/SUR2 potassium channels. 相似文献
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Temperature effects on very slow desorption of native chlorobenzenes from sediment to water 总被引:2,自引:0,他引:2
ten Hulscher TE Vrind BA van Noort PC Govers HA 《Environmental toxicology and chemistry / SETAC》2004,23(7):1634-1639
The temperature dependence of the kinetics of very slow desorption of eight chlorobenzenes was studied in laboratory batch experiments on a field-contaminated sediment from Lake Ketelmeer, The Netherlands. The observed rate constants for very slow desorption averaged (1.5 +/- 0.4) x 10(-4)/h at 10 degrees C, (2.9 +/- 1.0) x 10(-4)/h at 20 degrees C, (5.8 +/- 2.4) x 10(-4)/h at 35 degrees C, and (6.4 +/- 3.0) x 10(-4)/h at 45 degrees C over all eight compounds. Activation energies for desorption to water were close to the enthalpy for dissolution of the pure solid in water. The activation energies ranged from 18 to 53 kJ/mol with an average of 36 +/- 11 kJ/mol. These values confirm earlier reported activation energies for very slow desorption to water. They are much less than values for activation energies for desorption to the gas phase. That difference can be explained in terms of rate limiting desorption from carbonaceous adsorption sites. 相似文献
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Besselink HT Schipper C Klamer H Leonards P Verhaar H Felzel E Murk AJ Thain J Hosoe K Schoeters G Legler J Brouwer B 《Environmental toxicology and chemistry / SETAC》2004,23(12):2781-2789
In the Fourth National Policy Document on Water Management in The Netherlands, it is defined that in 2003, in addition to the assessment of chemical substances, special guidelines for the assessment of dredged material should be recorded. The assessment of dredged material is based on integrated chemical and biological effect measurements. Among others, the DR CALUX (dioxin responsive-chemically activated luciferase expression) bioassay has tentatively been recommended for inclusion in the dredged material assessment. To ensure the reliability of this bioassay, an intra- and interlaboratory validation study, or ring test, was performed, organized by the Dutch National Institute for Coastal and Marine Management (RIKZ) in cooperation with BioDetection Systems BV (BDS). The intralaboratory repeatability and reproducibility and the limit of detection (LOD) and quantification (LOQ) of the DR CALUX bioassay were determined by analyzing sediment extracts and dimethyl sulfoxide (DMSO) blanks. The highest observed repeatability was found to be 24.1%, whereas the highest observed reproducibility was calculated to be 19.9%. Based on the obtained results, the LOD and LOQ to be applied for the bioassay are 0.3 and 1.0 pM, respectively. The interlaboratory calibration study was divided into three phases, starting with analyzing pure chemicals. During the second phase, sediment extracts were analyzed, whereas in the third phase, whole sediments had to be extracted, cleaned, and analyzed. The average interlaboratory repeatability increased from 14.6% for the analysis of pure compound to 26.1% for the analysis of whole matrix. A similar increase in reproducibility with increasing complexity of handlings was observed with the interlaboratory reproducibility of 6.5% for pure compound and 27.9% for whole matrix. The results of this study are intended as a starting point for implementing the integrated chemical-biological assessment strategy and for systematic monitoring of dredged materials and related materials in the coming years. 相似文献
25.
Estimating non-response bias in a survey on alcohol consumption: comparison of response waves 总被引:1,自引:0,他引:1
Lahaut VM Jansen HA van de Mheen D Garretsen HF Verdurmen JE van Dijk A 《Alcohol and alcoholism (Oxford, Oxfordshire)》2003,38(2):128-134
AIMS: According to 'the continuum of resistance model' late respondents can be used as a proxy for non-respondents in estimating non-response bias. In the present study, the validity of this model was explored and tested in three surveys on alcohol consumption. METHODS: The three studies collected their data by means of mailed questionnaires on alcohol consumption whereby two studies also performed a non-response follow-up. RESULTS: Comparisons of early respondents, late respondents and non-respondents in one study showed some support for 'the continuum of resistance model', although another study could not confirm this result. Comparison of alcohol consumption between three time response groups showed no significant linear pattern of differences between response waves. CONCLUSIONS: The hypothesis that late respondents are more similar to non-respondents than early respondents, could not be confirmed or rejected. Repeated mailings are effective in obtaining a greater sample size, but seem ineffective in improving the representativeness of alcohol consumption surveys. 相似文献
26.
Lucci LM Anderson RL Harrie RP Mamalis N Coffin C Crandall DC 《Ophthalmic plastic and reconstructive surgery》2001,17(5):369-373
PURPOSE: Solitary fibrous tumor is a rare spindle-cell tumor that usually is seen in the pleura. The orbit is one of the most common extrapleural sites. It is frequently misdiagnosed as hemangiopericytoma and is seen in older patients. We present the youngest case of this tumor, which was apparent in family photographs by age 10 and removed at age 15. The first reported echography findings are presented. METHODS: Case report and literature review. RESULTS: Solitary fibrous tumor was diagnosed by microscopy and immunohistochemical study that showed cells reactive with vimentin and CD34. CONCLUSIONS: Solitary fibrous tumor of the orbit has been diagnosed with increasing frequency in recent years as the result of improved methods of pathologic examination. It is important to be aware of this tumor and recognize that it must be included in the differential diagnosis of highly vascular spindle-cell tumors even in young children. 相似文献
27.
Expression of p73, a novel protein related to the p53 tumour suppressor p53, and apoptosis in cholangiocellular carcinoma of the liver. 总被引:13,自引:0,他引:13
A Tannapfel K Engeland L Weinans A Katalinic J Hauss J M?ssner Ch Wittekind 《British journal of cancer》1999,80(7):1069-1074
p73, the first homologue of the tumour suppressor protein p53, was recently discovered on chromosome 1p36 and has been shown to induce apoptosis in a p53-like manner. The present study was performed with the aim of investigating the expression of p53, its new homologue p73 and the occurrence of apoptosis in cholangiocellular carcinoma. Protein levels of p73 were examined in 41 patients with curatively (R0-) resected cholangiocellular carcinomas with an antiserum, raised against a peptide in the N-terminal domain of p73. The incidence of mutations in the p53 gene was analysed by direct sequencing and also immunohistochemically. Apoptotic cell death was assessed using in-situ end-labelling (ISEL) technique in combination with morphological criteria. The results obtained were correlated with patient survival. Immunostaining of p73 protein was detected in 17/41 carcinomas examined (41%). The immunoreactivity was confined to the cell nucleus. In 15/41 patients (37%), mutations of the p53 gene were observed. Eleven out of these 15 patients stained also positive for p73. In contrast, out of 26 patients without any detectable p53 mutation, only six exhibited p73 immunostaining. We failed to observe a correlation between p73 expression or p53 and apoptosis within a given tumour. Survival analysis including the parameters stage and grade of disease, p73 and p53, and also apoptosis, showed that tumour stage and grade as well as p53 and p73 were significantly related to prognosis. In Cox regression survival analysis, however, only extent of primary tumour and lymph node status had an independent prognostic impact. Our results with a high prevalence of p73 within tumours harbouring mutated p53 gene suggest that p73 could compensate for p53 function. We failed to establish p73 or p53 as independent prognostic factors in cholangiocellular carcinoma of the liver. 相似文献
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Irmgard Henning-de Jong Ad M.J. Ragas Harrie W.M. Hendriks Mark A.J. Huijbregts Leo Posthuma Arjen Wintersen A. Jan Hendriks 《Ecotoxicology and environmental safety》2009,72(8):2037-2045
The present study aims to support decisions on whether or not to perform an extra toxicity test in order to improve environmental quality standards (EQSs). The impact of an additional ecotoxicity test was analyzed by predicting new ecotoxicity values with three different estimation methods and adding them to existing species sensitivity distributions (SSDs) on which the EQSs are based. The results show that EQSs are likely to increase due to increasing sample size, but the change also depends on the number of toxicity values available, the estimation method used and the representativeness of the species tested. The management consequences are illustrated in a case study on contaminated freshwater sediment in the Netherlands. It is shown that a slight increase of the EQS can result in a large reduction of sediment remediation costs without impairing regulatory protection levels. The paper identifies indicators that can be used to evaluate the potential impact of an extra ecotoxicity test. 相似文献