全文获取类型
收费全文 | 823篇 |
免费 | 30篇 |
国内免费 | 8篇 |
专业分类
耳鼻咽喉 | 23篇 |
儿科学 | 32篇 |
妇产科学 | 18篇 |
基础医学 | 99篇 |
口腔科学 | 30篇 |
临床医学 | 115篇 |
内科学 | 141篇 |
皮肤病学 | 14篇 |
神经病学 | 45篇 |
特种医学 | 108篇 |
外科学 | 63篇 |
综合类 | 7篇 |
预防医学 | 41篇 |
眼科学 | 22篇 |
药学 | 78篇 |
肿瘤学 | 25篇 |
出版年
2021年 | 12篇 |
2019年 | 14篇 |
2018年 | 4篇 |
2017年 | 5篇 |
2016年 | 4篇 |
2015年 | 9篇 |
2014年 | 13篇 |
2013年 | 17篇 |
2012年 | 24篇 |
2011年 | 20篇 |
2010年 | 36篇 |
2009年 | 23篇 |
2008年 | 38篇 |
2007年 | 33篇 |
2006年 | 31篇 |
2005年 | 25篇 |
2004年 | 36篇 |
2003年 | 22篇 |
2002年 | 21篇 |
2001年 | 18篇 |
2000年 | 18篇 |
1999年 | 16篇 |
1998年 | 25篇 |
1997年 | 27篇 |
1996年 | 16篇 |
1995年 | 21篇 |
1994年 | 21篇 |
1993年 | 16篇 |
1992年 | 14篇 |
1991年 | 17篇 |
1990年 | 15篇 |
1989年 | 21篇 |
1988年 | 17篇 |
1987年 | 21篇 |
1986年 | 24篇 |
1985年 | 13篇 |
1984年 | 17篇 |
1983年 | 10篇 |
1982年 | 13篇 |
1981年 | 8篇 |
1980年 | 13篇 |
1979年 | 13篇 |
1978年 | 6篇 |
1977年 | 8篇 |
1976年 | 9篇 |
1975年 | 13篇 |
1973年 | 5篇 |
1972年 | 7篇 |
1971年 | 8篇 |
1968年 | 4篇 |
排序方式: 共有861条查询结果,搜索用时 31 毫秒
1.
Mats Bergstrom Azita Monazzam Pasha Razifar Susan Ide Raymond Josephsson Bengt Langstrom 《Journal of nuclear medicine》2008,49(7):1204-1210
For a PET agent to be successful as a biomarker in early clinical trials of new anticancer agents, some conditions need to be fulfilled: the selected tracer should show a response that is related to the antitumoral effects, the quantitative value of this response should be interpretable to the antitumoral action, and the timing of the PET scan should be optimized to action of the drug. These conditions are not necessarily known at the start of a drug-development program and need to be explored. We proposed a translational imaging activity in which experiments in spheroids and later in xenografts are coupled to modeling of growth inhibition and to the related changes in the kinetics of PET tracers and other biomarkers. In addition, we demonstrated how this information can be used for planning clinical trials. METHODS: The first part of this concept is illustrated in a spheroid model with BT474 breast cancer cells treated with the heat shock protein 90 (Hsp90) inhibitor NVP-AUY922. The growth-inhibitory effect after a pulse treatment with the drug was measured with digital image analysis to determine effects on volume with high accuracy. The growth-inhibitory effect was described mathematically by a combined E(max) and time course model fitted to the data. The model was then used to simulate a once-per-week treatment; in these experiments the uptake of the PET tracers (18)F-FDG and 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) was determined at different doses and different time points. RESULTS: A drug exposure of 2 h followed by washout of the drug from the culture medium generated growth inhibition that was maximal at the earliest time point of 1 d and decreased exponentially with time during 10-12 d. The uptake of (18)F-FDG per viable tumor volume was minimally affected by the treatment, whereas the (18)F-FLT uptake decreased in correlation with the growth inhibition. CONCLUSION: The study suggests a prolonged action of the Hsp90 inhibitor that supports a once-per-week schedule. (18)F-FLT is a suitable tracer for the monitoring of effect, and the (18)F-FLT PET study might be performed within 3 d after dosing. 相似文献
2.
ALBERTO Q FARIAS LUCIANA L GONÇALVES EDUARDO LR CANÇADO ANTONIO C SEGURO SILVIA B CAMPOS CLARICE P ABRANTES-LEMOS FLAIR J CARRILHO 《Journal of gastroenterology and hepatology》2006,20(1):147-152
Background and Aims: Primary biliary cirrhosis (PBC) might be complicated by osteoporosis, whose etiology remains unknown but seems to be multifactorial. Prevalence rates of 30% to 60% for distal renal tubular acidosis (DRTA) have been reported in PBC patients, generally as incomplete DRTA. Although it is undisputed that a reduced bone mineral density (BMD) is the expected outcome among patients who have been suffering from longstanding chronic metabolic acidosis, it is unclear if incomplete DRTA is also associated with metabolic bone disease in PBC patients. The present study was undertaken to compare the BMD of PBC patients with and without DRTA.
Methods: The BMD of 23 PBC patients (11 with DRTA and 12 without), all with normal clearance of creatinine, was assessed by dual energy radiograph absorptiometry. The diagnosis of DRTA was made if the urine pH was above 5.4 in all samples after the oral acid overload, showing tubular inability to acidify urine in the presence of test-induced systemic metabolic acidosis.
Results: Densitometric signs of osteoporosis were found in 82% of DRTA cases and in 83% of patients without DRTA (difference not significant). There were no significant differences in BMD measurement, T and Z scores of patients with and without DRTA.
Conclusions: The present study could not support a correlation between the presence of DRTA and the bone loss observed in PBC patients. 相似文献
Methods: The BMD of 23 PBC patients (11 with DRTA and 12 without), all with normal clearance of creatinine, was assessed by dual energy radiograph absorptiometry. The diagnosis of DRTA was made if the urine pH was above 5.4 in all samples after the oral acid overload, showing tubular inability to acidify urine in the presence of test-induced systemic metabolic acidosis.
Results: Densitometric signs of osteoporosis were found in 82% of DRTA cases and in 83% of patients without DRTA (difference not significant). There were no significant differences in BMD measurement, T and Z scores of patients with and without DRTA.
Conclusions: The present study could not support a correlation between the presence of DRTA and the bone loss observed in PBC patients. 相似文献
3.
S G Lalka J M Malone D F Fisher V M Bernhard D Sullivan D Stoeckelmann R F Bergstrom 《Journal of vascular surgery》1989,10(5):501-9; discussion 509-10
This prospective study examined microbiologic features of arterial tissue and pharmacokinetics and bioactivity of cefamandole and cefazolin in patients undergoing elective primary prosthetic aortoiliofemoral/infrainguinal reconstruction. Double-blind, randomized, perioperative prophylaxis (1 gm intravenously every 6 hours for nine doses) with cefamandole or cefazolin was administered to 47 patients. Specimens of blood serum, subcutaneous fat, thrombus, atheroma, and arterial wall were obtained for culture and minimal inhibitory concentration and drug level analysis by high-pressure liquid chromatography. The serum half-life (hr +/- SEM) was 1.43 +/- 0.36 for cefamandole and 2.22 +/- 0.40 for cefazolin. Over the first 2 hours of surgery and for all time intervals combined, the serum concentration of cefazolin was significantly higher (p less than 0.025) than cefamandole. Irrespective of sampling time, the tissue concentration of cefazolin was significantly greater (p less than 0.005) than cefamandole. Positive arterial tissue cultures were obtained in 12 of 29 patients (41.4%) from 23 of 116 (19.8%) arterial tissue specimens. Coagulase-negative Staphylococcus was the predominant isolate, 64 of 93 (68.8%). Twenty-five of the 51 coagulase-negative staphylocci tested (49%) were slime-producers. During surgery, the arterial tissue concentration of cefamandole fell below the geometric mean minimal inhibitory concentration against all organisms combined, and against S. aureus (with the highest minimal inhibitory concentration of the prevalent isolates), significantly more often than the concentration of cefazolin. The data show that a significant number of primary elective aortoiliofemoral/infrainguinal reconstructions are associated with positive arterial tissue cultures, which represent a potential source of graft infection.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
4.
Neurophysiological investigation of effects of the D-1 agonist SKF 38393 on tonic activity of substantia nigra dopamine neurons 总被引:1,自引:0,他引:1
The effects of the D-1 agonist SKF 38393 on tonic activity of rat substantia nigra pars compacta dopamine neurons were studied using extracellular, single-unit recording techniques. Unlike nonselective D-1/D-2 dopamine agonists or the D-2 agonist quinpirole, SKF 38393 did not inhibit dopamine neuronal activity when applied iontophoretically or when administered intravenously in doses up to 20 mg/kg to chloral hydrate-anesthetized rats. Moreover, pretreatment with SKF 38393 did not alter the inhibitory response of these neurons to apomorphine or the D-2 agonist quinpirole. However, in locally anesthetized, gallamine-treated, artificially respired rats, dopamine cell activity was significantly altered by i.v. administration of SKF 38393; firing rate increases and decreases were observed. Administration of the inactive enantiomer of SKF 38393, S-SKF 38393, did not induce similar changes in parallel experiments. These results support the idea that unlike D-2 autoreceptor stimulation, D-1 receptor stimulation does not exert a direct local effect on dopamine neurons in the substantia nigra pars compacta and suggest that D-1 receptor stimulation at sites postsynaptic to the dopamine cells may indirectly affect the activity of some dopamine neurons through long-loop feedback mechanisms. 相似文献
5.
6.
7.
Alvestrand A.; Gutierrez A.; Bucht H.; Bergstrom J. 《Nephrology, dialysis, transplantation》1988,3(5):624-631
The effect of blood pressure reduction on the progression rateof chronic renal failure (CRF) was studied in 28 patients withCRF of diverse aetiology entering a prospective study (observationtime 724 months, mean 16 months). Endogenous creatinineclearance was 1266 ml/mm (mean 30±3 ml/mm). Weaimed to keep the blood pressure below 160/90 mmlHg. Dietaryprotein was not restricted. The progression rate of CRF wasassessed from the regression coefficients of the regressionsof creatinine clearance and the inverse of s-creatinine, respectively,on time. Progression rate and the means of all recordings ofmean arterial blood pressure (MAP) and urinary protein excretion,respectively, in each patient during the prospective phase werecompared with retro spective data from the proceeding period(observation time 425 months, mean 19 months). The patientsreceived various combinations of antihypertensive drugs includingdiuretics, beta-blockers and vasodilatory drugs. In 19 patientsMAP decreased from 109±2 to 102±2 mmHg (groupI), whereas MAP increased from 105±2 to l08±2mmHgin nine patients (group II). In group I proteinuria was significantlylower (P<0.05) and the progression of CRF was approximately50% slower (P.<0.01) in the prospective phase than in theretrospective phase; no changes were observed in group II. Calculatedfor all patients, significant correlations were observed betweenthe change in MAP and the change in progression rate and proteinexcretion, respectively. These results indicate that loweringof blood pressure results in decreased proteinuria and retardationof the progression of CRF irrespective of the aetiology. 相似文献
8.
Prior studies have shown that pneumothorax is one of the more difficult entities to diagnose with digitized radiography. This study was designed to test whether increasing resolution from 1.25 to 2.5 line pairs per millimeter (lp/mm) and image processing (edge enhancement from unsharp masking) would increase accuracy and confidence in the diagnosis of pneumothorax, as well as normal cases and other forms of lung disease. Conventional radiographs were digitized with use of a laser reader and then reformatted as film hard copy. Eleven observers read 35 cases reformatted in three different ways (1.25 lp/mm, 2.5 lp/mm, 1.25 lp/mm unsharp mask). The images with finer resolution (2.5 lp/mm) and unsharp mask images were superior to those with coarser resolution (1.25 lp/mm) for the diagnosis of pneumothorax. There was no difference in diagnostic accuracy for normal patients. For abnormalities other than pneumothorax, the unsharp mask images were significantly worse. Confidence in the diagnosis of pneumothorax and other abnormalities was highest with the finest resolution (2.5 lp/mm). 相似文献
9.
Observations on two members of the Swedish family with congenital dyserythropoietic anaemia,type III
S. N. Wickramasinghe A. Wahlin D. Anstee S. F. Parsons G. Stopps I. Bergstrom M. Eriksson H. Sandstrom S. Shiels 《European journal of haematology》1993,50(4):213-221
Abstract: Two affected individuals of the Swedish family with CDA, type III, in which the disease is transmitted as an autosomal dominant character, were studied. Both cases displayed features hitherto undescribed in this family but described in patients with CDA, type III, in whom the inheritance may have been as an autosomal recessive character. Such features were: (a) haemosiderinuria, (b) grossly disorganised erythroblast nuclei, (c) differences in the ultrastructural appearances of individual nuclei within the same multinucleate erythroblast and (d) intraerythroblastic inclusions resembling precipitated globin chains. In both cases the giant mononucleate erythroblasts and the multinucleate erythroblasts had total DNA contents up to 28c (1c = haploid DNA content) and 48c respectively, and some DNA synthesising bi- and multinucleate erythroblasts contained one or more nuclei which were unlabelled with 3H-thymidine. These findings are similar to those in patients with the autosomal recessive type of disease. Thus no major phenotypic differences are yet apparent between cases of CDA, type III, with different patterns of inheritance. Analysis of the surface erythrocyte proteins of the 2 Swedish CDA, type III, patients with monoclonal antibodies recognising Band 3, glycophorins A, B, C and D, Rh, CD44, CD47, CD55, CD58, CD59, Lutheran, Kell, LW and acetylcholinesterase did not reveal any gross abnormality of expression of these proteins. A slightly altered expression of blood group antigens A and H was revealed by the lectins Dolichos biflorus and Ulex europaeus and the Mr of Band 3 as judged by SDS polyacrylamide gel electrophoresis was also slightly reduced, suggesting that there may be minor alterations in the degree of N-glycosylation of some red cell membrane constituents. 相似文献
10.
MGC Hendriks P Dogterom JT Ebels B Oosterhuis LR Geertsema T Hulot G Bianchetti and JHG Jonkman 《Fundamental & clinical pharmacology》1998,12(5):559-565
Summary— In the present study we have compared the steady state biopharmaceutic characteristics of four diltiazem once daily controlled release capsules: Mono-Tildiem LP 300® (300 mg), Adizem® XL (300 mg)1, Cardizem® (300 mg) and Dilacor® (240 mg). Sixteen healthy male volunteers (aged 22.9 ± 3.3 years, range 19–31 years) completed an open label, multiple oral dose, randomized, four-period crossover study without a washout period in between. The volunteers received each diltiazem formulation once daily for four days. Trough diltiazem and metabolites plasma concentrations were determined on days 3 and 4. The 24-h plasma concentration-time profiles were assessed after the dose on day 4 of each period. The following steady state pharmacokinetic parameters for diltiazem were calculated: the minimum plasma concentration (cmin), the maximum plasma concentration (cmax), the time to reach that concentration (tmax), the time interval during which the plasma concentration exceeds 50% of cmax (t50), the area under the plasma concentration-time curve (AUC72–96) and the peak-to-trough fluctuation (PTF). For the metabolites of diltiazem, N-mono-desmethyl-diltiazem (NDM) and desacetyldiltiazem (DAD), AUC72–96 (AUCNDM and AUCDAD) and the ratio metabolite/parent compound were calculated. Steady state was achieved on day 3. Except one, all controlled release formulations have satisfactory controlled release properties allowing once daily administration. However, significant (P < 0.05) differences were found between the pharmacokinetic characteristics which do not allow exchange of the various formulations. Concentrations well below 50 ng·mL-1 in the morning hours were observed for Dilacor® (240 mg) and Adizem® XL (300 mg), which could be a disadvantage of these formulations as it is well-known that ischaemic events occur at a higher rate during that part of the day. The plasma concentration profiles of NDM and DAD, the major circulating metabolites, parallel the plasma concentration profiles for the parent compound. From a clinical point of view, all treatments were well tolerated. 相似文献