全文获取类型
收费全文 | 163篇 |
免费 | 9篇 |
专业分类
儿科学 | 4篇 |
基础医学 | 8篇 |
临床医学 | 30篇 |
内科学 | 32篇 |
神经病学 | 14篇 |
外科学 | 15篇 |
综合类 | 8篇 |
预防医学 | 11篇 |
眼科学 | 4篇 |
药学 | 23篇 |
肿瘤学 | 23篇 |
出版年
2023年 | 1篇 |
2021年 | 2篇 |
2020年 | 1篇 |
2019年 | 1篇 |
2018年 | 1篇 |
2015年 | 1篇 |
2014年 | 3篇 |
2013年 | 2篇 |
2012年 | 6篇 |
2011年 | 4篇 |
2010年 | 4篇 |
2009年 | 3篇 |
2008年 | 12篇 |
2007年 | 6篇 |
2006年 | 5篇 |
2005年 | 5篇 |
2004年 | 7篇 |
2003年 | 7篇 |
2002年 | 8篇 |
2001年 | 8篇 |
2000年 | 6篇 |
1999年 | 7篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1990年 | 5篇 |
1989年 | 2篇 |
1988年 | 5篇 |
1987年 | 8篇 |
1986年 | 4篇 |
1985年 | 7篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1977年 | 5篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1974年 | 3篇 |
1973年 | 4篇 |
1972年 | 1篇 |
1971年 | 2篇 |
1968年 | 1篇 |
排序方式: 共有172条查询结果,搜索用时 15 毫秒
1.
2.
M. C. Winslet M. J. Webberley V. Melikian I. A. Donovan 《Postgraduate medical journal》1993,69(815):744-746
Spontaneous rupture of the spleen is rare and has not been previously reported in association with idiopathic thrombocytopaenic purpura. Its rarity makes familiarity with its presentation difficult and may result in a potentially fatal delay in diagnosis and treatment. 相似文献
3.
Melikian Assieh A.; Leszczynska Joanna M.; Hecht Stephen S.; Hoffmann Dietrich 《Carcinogenesis》1986,7(1):9-15
We have studied the effects of the co-carcinogen catechol (1,2-dihydroxybenzene)on the metabolic activation of [3H] benzo[a]pyrene (BaP) inmouse skin, in vivo and on the binding of BaP metabolites toDNA and protein at intervals from 0.524 h. Upon topicalapplication of 0.015 mg [3H]BaP and 0.25 or 0.5 mg catecholper mouse, catechol had little effect on the total amount of[3H]BaP metabolized in mouse skin, but it affected the relativeproportions of [3H]BaP metabolites. Catechol (0.5 mg/mouse)decreased the proportion of watersoluble [3H]BaP metabolites,ethyl acetate-soluble polar metabolites and quinones, but doubledthe levels of unconjugated 3-hydroxy-BaP at all measured intervalsafter treatment. Catechol also caused a small increase in thelevels of trans-7,8-dihydroxy-7,8-dihydroBaP and trans-9,10-dihydroxy-9,10-dihydroBaP0.5 h after treatment. Two hours after treatment, the levelsof these metabolites subsided to those of the controls. Catecholdid not affect the levels of glutathione conjugates of BaP.However, it caused a decrease in glucuronide and sulphate conjugateformation from BaP. Catechol caused an 2-fold increase in theformation of anti-7, 8-dihydroxy-9, 10-epoxy-7, 8, 9, 10-tetrahydroBaP(BPDE) DNA adducts and elevated the ratio of anti-syn-BPDE-DNAadducts 1.6 to 2.9-fold. Catechol treatment increased the radioactivityassociated with epidermal proteins after [3H]BaP application.Because catechol increased levels of 3-hydroxyBaP, we consideredthe possibility that 3-hy-droxyBaP might enhance the tumor initiatingactivities of BaP or BPDE in mouse skin; a bioassay demonstratedthat this was not the case. The results of this study indicatethat one important effect of catechol related to its co-carcinogenicityis its ability to enhance formation of anti-BPDE-DNA adductsin mouse skin. 相似文献
4.
5.
Melikian AG Shakhnovich AR Arutiunov NV 《Zhurnal voprosy ne?rokhirurgii imeni N. N. Burdenko》2002,(4):5-11; discussion 11
The paper presents data of a retrospective analysis of the outcomes of endoscopic ventriculostomy of the 3rd ventricle, obtained in a consecutive series of 120 patients aged 5 months to 58 years who had occlusive hydrocephalus and operated on at the Research Institute of Neurosurgery, Russian Academy of Medical Sciences, in 1995-2000. In most cases (n = 112), hydrocephalus was caused by a block at the level of the cerebral aqueduct. In more than 50% of the patients, different tumors were responsible for occlusion. In 96 (80%) cases, the operation led to the elimination of occlusion and to the regression of symptoms just after surgery. Complications were few and observed in 19 patients, ventriculitis (n = 7) and intracranial hemorrhages (n = 6) being most common. No death occurred. Seventy three patients were followed up for 1 month to 5 years (mean 1.5 years). Eliminated occlusion and steady-state remission were found in 64 (87.7%) cases. Improvement was strongly correlated with an increase in the reserve craniovertebral content capacity estimated by measuring the pulse amplitude of blood flow in the tentorial sinus in body position-changing tests. In 9 patients, the symptoms of hydrocephalus remained or recurred after short-term improvement. In 3 of them, this occurred with anatomically competent anastomoses between the 3rd ventricle and cisterns. In the other 6 cases, the obliteration and anatomic incompetence of ventriculostoma were responsible for a relapse. In 8 of the 9 patients, shunting had to be made subsequently in the period of 1 to 6 months. The paper also considers some biophysical aspects of cerebrospinal fluid circulation and discusses indications for endoscopy. It is concluded that endoscopic ventriculostomy of the 3rd ventricle is the method of choice in the treatment of patients with obstructive hydrocephalus. 相似文献
6.
K R Thien J A Blair R J Leeming W T Cooke V Melikian 《Journal of clinical pathology》1977,30(5):438-448
In an aseptic microbiological assay of folate compounds and their breakdown compounds, using Lactobacillus casei, Streptococcus faecalis, and Pediococcus cerevisiae, 4a-hydroxy-5methyl-4,5,6,7-tetrahydrofolate and 5-methyl-5,8-dihydrofolate were inactive under all conditions to all three organisms and 5-methyl-5,6-dihydrofolate was inactive unless ascorbate was present in the incubation medium, and then only to L. casei. 5-Methyltetrahydrofolate was active only for L. casei, and activity in purified samples to S. faecalis was due to trace amounts of folic acid. Analysis of S. faecalis values in the serum in normal subjects and in patients with various disorders showed that levels of 10-formyltetrahydrofolate are raised in coeliac disease, leukaemia, rheumatoid arthritis, and schizophrenia. 5-Methyltetrahydrofolate is readily absorbed by normal human subjects and by patients with pernicious anaemia but poorly absorbed by patients with coeliac disease or leukaemia. 5-Methyl-5,6-dihydrofolate was quickly absorbed by normal human subjects, being reflected by a considerably raised level of 5-methyltetrahydrofolate in serum when sodium bicarbonate was given by mouth before the 5-methyl-5,6-dihydrofolate. These higher levels were comparable to those in patients with pernicious anaemia after oral administration of 5-methyl-5,6-dihydrofolate. Oral 5-methyl-5,8-dihydrofolate and 4a-hydroxy-5-methyl-tetrahydrofolate did not appear as microbiologically active folates in the serum. The findings of this study suggest that the availability for biological utilisation of the major dietary folate compounds will depend on the amount of gastric acidity and of ascorbate in the intestinal chyme. Many may be unavailable for metabolic utilization in the body. 相似文献
7.
5-Methylcbrysene (5-MeC) can form two bay region dihydrodiolepoxides: 1,2-dihydroxy-3-4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene(DE-I) which has the methyl group and the epoxide ring in thesame bay region, and 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro-5-methylchrysene(DE-II). In a previous study, we observed that the ratio ofDE-I:DNA adduds to DE-II:DNA adducts in mouse epidermis, 24h after application of [3H]5-MeC metabolites was 2.7 to 1. Toinvestigate the basis for this observation we have now studied:(i) the formation of [3H]5-MeC in mouse epidermis in vivo atvarious time intervals from 0.33 to 24 h; (ii) the persistenceof DE-I:DNA adducts and DE-II:DNA adducts in mouse epidermisat 448 h after application of [3H]5-MeC and (iii) thereactions of DE-I and DE-II with calf thymus DNA in vitro. Incontrast to results obtained with mouse liver 9000 g supernatant,the dihydrodiol precursors of DE-I and DE-II were present inequivalent quantities in mouse epidermis in vivo at every timepoint studied. The ratio of DE-I:DNA adducts to DE-II:DNA adductsin mouse epidermis was constant throughout the time period studied.However, the extent of formation of DE-I:DNA adducts was greaterthan that of DE-II:DNA adducts upon reaction of DE-I or DE-IIwith calf thymus DNA in vitro. These results suggest that differencesin reactivity with DNA of DE-I and DE-II may be responsiblefor the higher levels in mouse epidermis of DE-I:DNA adductscompared with DE-II:DNA adducts and provide a possible basisfor the observed enhancing effect of a bay region methyl groupon the carcinogenicity of polynuclear aromatic hydrocarbons. 相似文献
8.
Chen KM El-Bayoumy K Cunningham J Aliaga C Li H Melikian AA 《Chemical research in toxicology》2004,17(3):370-377
Benzene, a constituent of cigarette smoke, is a human leukemogen and induces bone marrow toxicity. The mechanism of benzene-induced toxicity is not well-established. We hypothesized that relatively high levels of nitric oxide formed in bone marrow can react with oxygen and/or superoxide anion that is generated during redox cycling of ring-hydroxylated benzene metabolites to yield peroxynitrite as well as other NO-derived intermediates. Peroxynitrite can either directly damage cellular macromolecules or form nitrated toxic metabolites. Toward this end, we investigated whether nitro derivatives of benzene are formed in bone marrow of mice treated with benzene. First, we have characterized products formed during activation of benzene in Fenton's system in the absence or presence of NO-releasing compound in vitro by GC/MS. The result of above experiment prompted us to determine whether similar products can be formed in vivo. Groups of B6C3F1 male mice, eight weeks of age, were given a single intraperitoneal dose of [14C]benzene (400 mg/kg body wt, 9.7 mCi/mmol) or an equal dose of unlabeled benzene in corn oil, and the mice were killed 0.5 or 1 h posttreatment. The control group received only vehicle injections. Organic solvent extractable metabolites from bone marrow, liver, lungs, and blood of mice treated with [14C]benzene were identified by comparison of their respective retention times under two different HPLC conditions with authentic standard samples. These metabolites were further characterized by comparison of their GC/MS properties to those of reference standards. Nitro metabolites, namely, nitrobenzene, nitrobiphenyl, and nitrophenol isomers, were detected in the bone marrow of the mice 1 h after benzene treatment. Formation of nitro derivatives in other tissues was either not observed or was significantly less than that formed in bone marrow. This study clearly demonstrates that nitric oxide is a contributor to benzene metabolism and can form nitrated derivatives that may, in part, account for bone marrow toxicity. 相似文献
9.
Shi J Ludden TM Melikian AP Gastonguay MR Hinderling PH 《Journal of pharmacokinetics and pharmacodynamics》2001,28(6):555-575
Aims: To derive useful pharmacokinetic (PK) and pharmacodynamic (PD) information for guiding the clinical use of sotalol in pediatric patients with supraventricular (SVT) or ventricular tachyarrhythmia (VT).Methods: Two studies were conducted in-patients with SVT or VT in the age range between birth and 12 years old. Both studies used an extemporaneously compounded formulation prepared from sotalol HCl tablets. In the PK study, following a single dose of 30 mg/m2 sotalol, extensive blood samples (n=10) were taken. The PK–PD study used a dose escalation design with doses of 10, 30, and 70 mg/m2, each administered three times at 8-hr intervals without a washout. Six ECG recordings for determination of QT and RR were obtained prior to the initial dose of sotalol. Four blood samples were collected six ECG's were determined during the third interval at each dose level. Plasma concentrations of sotalol (C) were assayed by LC/MS/MS. The data analysis used NONMEM to obtain the population PK and PD parameter estimates. The individual PK and PD parameters were estimated with empirical Bayes methodology.Results: A total of 611 C from 58 patients, 477 QTc and 499 RR measurements from 23 and 22 patients, respectively, were available for analysis. The PK of sotalol was best described by a linear two-compartment model. Oral clearance (CL/F) and volume of central compartment (Vc/F) were linearly correlated with body surface area (BSA), body weight or age. CL/F was also linearly correlated with creatinine clearance. The best predictor for both CL/F and Vc/F was BSA. The remaining intersubject coefficients of variation (CV's) in CL/F, and Vc/F were 21.6% and 20.3%, respectively. The relationship of QTc to C was adequately described by a linear model. The intersubject CV's in slope (SL) and intercept (E0) were 56.2 and 4.7%, respectively. The relationship of RR to C was also adequately described by a linear model in which the baseline RR and SL were related to age or BSA. The intersubject CV's for SL and E0 were 86.7 and 14.4%, respectively.Conclusions: BSA is the best predictor for the PK of sotalol. Both QTc and RR effects are linearly related to C. No covariates are found for the QTc–C relation, while the RR–C relation shows age or BSA dependency. 相似文献
10.
Nikitin EA Lorie IuIu Melikian AL Samoĭlova RS Bulycheva TI Obukhova TN Kaplanskaia IB Doronin VA Kolosova LIu Goriacheva SR 《Terapevticheski? arkhiv》2003,75(7):38-47
AIM: To assess factors of an unfavourable prognosis in a group of intermediate risk of B-cell chronic lymphoid leukemia (BCCLL). MATERIAL AND METHODS: 206 BCCLL patients (mean age 55.5 years, male/female = 1.66) entered the study conducted by Hematological Research Center in 1992-2000. RESULTS: Nine patients under 35 years of age did not survive 5 years except one female who achieved a complete remission on fludarabin. The type of bone marrow infiltration (diffuse vs interstitial and nodular), the time of lymphocyte count doubling (under or over 12 months) discriminate the patients by prognosis in the group of intermediate risk: medians of overall survival 65 months vs 148 months and 72 vs 133 months, respectively (p < 0.005 for both curves, log-rank criterion). Survival medians in groups with low (< 50% cells) and high (> 50% cells) expression of CD38+ cells in the group of intermediate BCCLL risk comprise 55 and 106 months (p = 0.005). The type of bone marrow infiltration and time of doubling of lymphocyte count overlap: > 70% patients with a diffuse type of bone marrow infiltration have the time of doubling under 12 months and vice versa while expression of CD38 do not overlap with these values. Combination of two signs (type of bone marrow infiltration and CD38 expression or time og lymphocyte count doubling and CD38 expression) allows more precise identification of prognostically unfavourable groups. Medians of survival for combination of the first two signs (two positive against two negative) comprise 51 months vs 169 months (p < 0.0001), for combination of the latter two signs 55 months vs 106 months was not reached (p < 0.001). Although most patients with a tumor form of BCCLL are referred to stage II, the prognosis in this form is much worse than in stage II, survival medians are 44 and 69 months, respectively (p < 0.05). A mutation status of the genes of a variable region of immunoglobulins enable identification of the group of patients with a relatively benign course of BCCLL (survival medians 61 and 289 months, p < 0.0001). CONCLUSION: In patients under 35 years of age BCCLL runs unfavourably and seems to require intensive polychemotherapy. Usage of a combination of the signs (CD38, time of doubling of lymphocyte count and type of bone marrow infiltration) is a simple and reliable method of identification of prognostically different categories of patients in the group of an intermediate BCCLL risk. Prognosis in patients with a tumor form of BCCLL is unfavourable: medians of survival in patients with a tumor form and stage III-IV are comparable. Mutational status of the genes of immunoglobulin variable region may serve a marker of a long-term prognosis. 相似文献