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排序方式: 共有119条查询结果,搜索用时 15 毫秒
91.
92.
Hidalgo M Bruckheimer E Rajeshkumar NV Garrido-Laguna I De Oliveira E Rubio-Viqueira B Strawn S Wick MJ Martell J Sidransky D 《Molecular cancer therapeutics》2011,10(8):1311-1316
Patients with many advanced solid cancers have very poor prognosis, and improvements in life expectancy are measured only in months. We have recently reported the remarkable clinical outcome of a patient with advanced, gemcitabine-resistant, pancreatic cancer who was later treated with DNA-damaging agents, on the basis of the observation of significant activity of this class of drugs against a personalized tumorgraft generated from the patient's surgically resected tumor. Here, we extend the approach to patients with other advanced cancers. Tumors resected from 14 patients with refractory advanced cancers were propagated in immunodeficient mice and treated with 63 drugs in 232 treatment regimens. An effective treatment regimen in the xenograft model was identified for 12 patients. One patient died before receiving treatment, and the remaining 11 patients received 17 prospectively guided treatments. Fifteen of these treatments resulted in durable partial remissions. In 2 subjects, no effective treatments were found. Overall, there was a remarkable correlation between drug activity in the model and clinical outcome, both in terms of resistance and sensitivity. The data support the use of the personalized tumorgraft model as a powerful investigational platform for therapeutic decision making and to efficiently guide cancer treatment in the clinic. 相似文献
93.
Rajeshkumar NV Pillai MR Kuttan R 《Journal of experimental & clinical cancer research : CR》2003,22(2):201-212
Plant-derived phenolic compounds manifest many beneficial effects and can potentially inhibit several stages of carcinogenesis. In the present study, we investigated the efficacy of Emblica officinalis (E. officinalis) polyphenol fraction (EOP) on the induction of apoptosis in mouse and human carcinoma cell lineses and its modulatory effect on N- nitrosodiethylamine (NDEA) induced liver tumors in rats. The results indicate that EOP treatment could induce apoptosis in Dalton's Lymphoma Ascites (DLA) and CeHa cell lines At 200 microg/ml dose EOP induced membrane blebbing, chromatin condensation and intenucleosomal breaks as evident from the morphology and DNA ladder pattern obtained in gel electrophoresis. The results also suggested that EOP treatment could decrease the liver tumour development induced by NDEA. Animals administered (oral) with NDEA (0.02%, 2.5 ml/rat, 5 days a week, 20 weeks) developed visible liver tumours by the end of the 20th week and the liver weight raised to 5.2 +/- 1.1 g/ 100 g body weight. Only 11% of the animals treated with EOP (60 mg/kg, oral, 5 days a week for 20 weeks) developed visible liver tumours by this period and the liver weights were reduced to 3.2 +/- 0.7 g/ 100 g body weight. gamma-glutamyl transpeptidase activity was raised to 88.4 +/- 16.2 U/l in serum of NDEA treated group was reduced to 48.4 +/- 14.8 U/l by EOP treatment. Elevated levels of serum alkaline phosphatase (ALP), glutamate pyruvate transaminase (GPT), bilirubin, liver glutathione S-transferase (GST) and glutathione (GSH) in the NDEA administered group were significantly reduced by EOP treatment. The EOP was found to scavenge superoxide and hydroxyl radicals and inhibit lipid peroxidation in vitro. EOP also inhibited DNA topoisomerase I in Saccharomyces cervisiae mutant cell cultures and the activity of cdc25 tyrosine phosphatase. 相似文献
94.
The incidence of painful crisis in homozygous sickle cell disease: correlation with red cell deformability 总被引:1,自引:0,他引:1
Lande WM; Andrews DL; Clark MR; Braham NV; Black DM; Embury SH; Mentzer WC 《Blood》1988,72(6):2056-2059
To determine whether the vasoocclusive severity of homozygous sickle cell (SS) disease is influenced by cellular dehydration, we correlated the incidence of painful crisis with steady-state measurements of red cell hydration. Sixteen children with SS disease were followed for 3.3 to 8 years (mean, 6.8 years), and a single crisis rate was calculated for each patient. At the time of well visits, cellular hydration was assessed by measuring cell deformability, the percentage of red cells with a density greater than or equal to 1.1056 g/mL, and the percentage of irreversibly sickled cells (ISC). The incidence of painful crisis showed a strong positive correlation with Omax, a deformability measurement reflecting cellular hydration (r = .84, P less than .002), and with hemoglobin concentration (r = .59, P = .04). That is, higher crisis rates were observed in patients with less dehydrated, more deformable red cells and also in patients with higher hemoglobin concentrations. Furthermore, cell deformability and hemoglobin concentration were independent predictors of the incidence of painful crisis, which is consistent with separate effects of these two red cells parameters on vasoocclusive severity. 相似文献
95.
Endothelins are potent endogenous vasoactive substances. We have found that intravenous administration of endothelin (ET)B receptor agonist, IRL 1620 (N-suc-[Glu9, Ala(11,15)]ET-1 (8-21)) to tumour bearing rats increases blood perfusion and enhances delivery of chemotherapeutic agents to the tumour tissue. This study was conducted to determine whether IRL 1620, an ET(B) receptor selective agonist, alters pharmacokinetics of paclitaxel in breast tumour bearing rats. Breast tumours were induced in female Sprague-Dawley rats by N-methyl-n-nitrosourea (50 mg kg(-1), i.p). Saline (0.3 mL kg(-1), i.v.) or IRL 1620 (3 nmol kg(-1), i.v.), was administered to the tumour bearing rats via the tail vein. Paclitaxel (3 mg kg(-1), i.v.) was administered 15 min after saline or IRL 1620 injection. Serial plasma samples were collected up to 10 h after paclitaxel administration and analysed using an HPLC-UV assay. In a similar study [3H]-paclitaxel (40 microCi, i.v.) was administered after saline or IRL 1620 injection as described above and serial plasma samples were collected until 24 h. Data was fitted to a three-compartment model and pharmacokinetic parameters were generated using WinNonlin software. The AUC(0-infinity) (9.42 +/- 3.18 microg h mL(-1)), clearance (0.69 +/- 0.17 L h(-1) kg(-1)), volume of distribution (10.31 +/- 4.54 L kg(-1)) and half life (1.00 +/- 0.32 h) of [3H]-paclitaxel in tumour rats were similar in rats treated with IRL 1620 or vehicle. Tumour concentration of [3H]-paclitaxel was determined in rats treated with IRL 1620 or vehicle and there was a significant increase in tumour paclitaxel concentration (308.59 +/- 24.42%) in rats treated with IRL 1620 compared with vehicle. It is concluded that IRL 1620, an ET(B) receptor agonist, does not alter paclitaxel pharmacokinetics and can selectively augment the delivery of paclitaxel to the tumour tissue. 相似文献
96.
Nickel-induced oxidative stress in testis of mice: evidence of DNA damage and genotoxic effects 总被引:6,自引:0,他引:6
Oxidative stress (OS) mechanisms are speculated to play a significant role in nickel-induced toxic effects and their carcinogenic potency. Although nickel-induced oxidative damage in somatic tissues is well demonstrated, evidence of the involvement of a similar mechanism(s) in nickel-induced testicular dysfunction and associated genotoxic effects is scarce. Hence, the present study aimed to investigate the nickel-induced OS response in testis and the associated genotoxic implications in vivo. Initially, the toxicity profile of nickel chloride was determined in adult albino mice (CFT-Swiss) following administration (intraperitoneal) of single doses. Subsequently, multiple sublethal doses (1.25, 2.5, and 5.0 micromol/100 g of body weight per day for 3 days) were used to characterize effects on testicular histoarchitecture, lipid peroxidation (LPO) in testis (homogenates, microsomal or mitochondrial fractions) and epididymal sperm, DNA damage, induction of apoptosis in testis, and incidence of sperm head abnormalities. Although short-term doses of nickel induced only a minimal LPO response, multiple doses elicited a moderate (15% to 30%) increase in LPO in whole homogenates and higher dose-related increases in both mitochondrial (20% to 50%) and microsomal fractions (25% to 60%). This was associated with a significant increase in DNA damage in the testis as evidenced by increased single-strand breaks (fluorimetric analysis of DNA unwinding assay). Further, at higher doses, nickel-induced apoptosis was demonstrable in the testis biochemically. Although caudal sperm counts determined at all sampling weeks showed no alterations, analysis for head abnormalities revealed a nearly 3- to 4-fold increase in the percentage of abnormal sperms among the nickel-treated males during the first 3 weeks. Furthermore, mating of nickel-treated (2.5 micromol/100 g of body weight per day for 5 days) males sequentially for a period of 5 weeks with untreated females resulted in a significant increase in male-mediated dominant lethal-type mutations (the frequency of dead implantations) during the first 3 weeks, suggesting a stage-specific effect on postmeiotic germ cells. These findings suggest that testicular toxicity of nickel compounds may be related to enhanced production of reactive oxygen species, probably mediated through oxidative damage to macromolecules, including damage to DNA. 相似文献
97.
98.
High dose vitamin A supplementation in the course of pneumonia in Vietnamese children 总被引:2,自引:0,他引:2
NV Si C. Grytter NNT Vy NB Hue FK Pedersen 《Acta paediatrica (Oslo, Norway : 1992)》1997,86(10):1052-1055
We carried out a randomized, placebo-controlled, double-blinded trial to evaluate the effect on morbidity of high dose oral vitamin A, given on hospital admission to 592 children aged 1–59 months with moderate and severe pneumonia. Severely underweight children were not included, but 45% were moderately underweight. The vitamin A and placebo groups were comparable in baseline characteristics. Four patients died. Among all of the surviving children, no differences were found regarding mean time for normalization of fever, respiratory rate and time of hospitalization. Stratification for moderate malnutrition, degree of pneumonia, age and sex revealed moderately malnourished vitamin A-supplemented children to have a shorter time of hospitalization ( p = 0. 04), due to an effect in females aged > 12 months ( p = 0. 02) and females with very severe pneumonia ( p = 0. 048). This study indicates that, in developing countries like Vietnam, supplementation with vitamin A in children with pneumonia could shorten the recovery rate in the ones that are undernourished, especially females > 1 y old. 相似文献
99.
Ooplasmic injection of elongating spermatids for the treatment of non- obstructive azoospermia 总被引:3,自引:12,他引:3
Sofikitis NV; Yamamoto Y; Miyagawa I; Mekras G; Mio Y; Toda T; Antypas S; Kawamura H; Kanakas N; Antoniou N; Loutradis D; Mantzavinos T; Kalianidis K; Agapitos E 《Human reproduction (Oxford, England)》1998,13(3):709-714
We applied the technique of ooplasmic elongating spermatid injection to the
treatment of non-obstructive azoospermia. Mature oocytes were injected with
elongating spermatids isolated from testicular biopsy material obtained
from 13 non-obstructed azoospermic men. Seventy-three oocytes were
successfully injected with elongating spermatids and were then cultured for
36 h. At 13 h post-injection 68 oocytes were found to be activated and 52
of them were fertilized. Forty-one 2- to 4-cell stage embryos developed
from normally fertilized oocytes were transferred. At least two embryos
were transferred to each female partner. Two pregnancies were achieved.
Elongating spermatid injection may have a role in the treatment of
non-obstructive azoospermia.
相似文献
100.
Robert W Ross Susan Halabi San-San Ou Barur R Rajeshkumar Bruce A Woda Nicholas J Vogelzang Eric J Small Mary-Ellen Taplin Philip W Kantoff 《Clinical cancer research》2005,11(22):8109-8113
PURPOSE: Analyzing metastatic prostate cancer tissue is of considerable importance in evaluating new targeted agents, yet acquiring such tissue presents a challenge due to the predominance of bone metastases. We assessed factors predicting a successful tumor harvest from bone marrow biopsies (BMBx) in castration-resistant metastatic prostate cancer patients. MATERIAL AND METHODS: Data from Cancer and Leukemia Group B study 9663 were reviewed. Bone marrow biopsies were obtained from 184 patients who underwent an office-based, unguided bone marrow biopsy of the posterior iliac crest. RESULTS: Forty-seven of the 184 patients (25.5%) had a positive bone marrow biopsy. When considered in a multivariate logistic regression analysis, lower hemoglobin levels, higher alkaline phosphatase, and higher lactate dehydrogenase levels were associated with a higher likelihood of a positive BMBx. The median survival time was 11 months (95% confidence interval, 8.0-14) among patients with a positive BMBx compared with 23 months (95% confidence interval, 19-27) with a negative BMBx. The median time to progression and time to prostate-specific antigen progression-free survival were also significantly decreased among positive BMBx patients. No patients with a positive BMBx survived beyond 3 years, whereas 11 of the 137 patients with a negative BMBx survived beyond 5 years. DISCUSSION: Using common laboratory values, a specific patient cohort can be defined from whom the yield of a nonguided BMBx would be high enough to justify this approach. For studies that require broader entry criteria, a more directed approach with image guidance is recommended. 相似文献