全文获取类型
收费全文 | 383篇 |
免费 | 31篇 |
国内免费 | 2篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 14篇 |
妇产科学 | 5篇 |
基础医学 | 47篇 |
口腔科学 | 25篇 |
临床医学 | 47篇 |
内科学 | 101篇 |
皮肤病学 | 7篇 |
神经病学 | 11篇 |
特种医学 | 68篇 |
外科学 | 39篇 |
综合类 | 6篇 |
预防医学 | 16篇 |
眼科学 | 2篇 |
药学 | 5篇 |
肿瘤学 | 22篇 |
出版年
2023年 | 1篇 |
2020年 | 2篇 |
2019年 | 2篇 |
2018年 | 7篇 |
2017年 | 6篇 |
2016年 | 6篇 |
2015年 | 8篇 |
2014年 | 10篇 |
2013年 | 14篇 |
2012年 | 5篇 |
2011年 | 9篇 |
2010年 | 19篇 |
2009年 | 14篇 |
2008年 | 7篇 |
2007年 | 12篇 |
2006年 | 18篇 |
2005年 | 15篇 |
2004年 | 6篇 |
2003年 | 10篇 |
2002年 | 6篇 |
2001年 | 9篇 |
2000年 | 8篇 |
1999年 | 14篇 |
1998年 | 23篇 |
1997年 | 18篇 |
1996年 | 18篇 |
1995年 | 13篇 |
1994年 | 10篇 |
1993年 | 10篇 |
1992年 | 9篇 |
1991年 | 2篇 |
1990年 | 5篇 |
1989年 | 17篇 |
1988年 | 8篇 |
1987年 | 6篇 |
1986年 | 7篇 |
1985年 | 6篇 |
1984年 | 5篇 |
1983年 | 7篇 |
1982年 | 6篇 |
1981年 | 11篇 |
1980年 | 6篇 |
1979年 | 3篇 |
1978年 | 4篇 |
1977年 | 5篇 |
1976年 | 4篇 |
1975年 | 4篇 |
1959年 | 1篇 |
排序方式: 共有416条查询结果,搜索用时 31 毫秒
1.
G Gaitanis K Nomikos E Vava EC Alexopoulos ID Bassukas 《Journal of the European Academy of Dermatology and Venereology》2009,23(12):1427-1431
Background/aim Theoretical considerations support the combination of cryosurgery and topical imiquimod to treat basal cell carcinomas (BCC). The aim of the present study was to test the feasibility and efficacy of 'cryosurgery during continued imiquimod application' ('immunocryosurgery') to treat 'high-risk-for-recurrence' BCCs.
Methods Thirteen patients with 21 biopsy-proven tumours (4 of 21 relapses after prior surgery) were included. After 2–5 weeks (median, 3) of daily 5% imiquimod cream application, the tumours were treated by liquid N2 cryosurgery (spray, two cycles, 10–20 s) and imiquimod was continued for additional 2–12 weeks (median, 4). The outcome after at least 18 months of follow-up (18–24 months) is currently reported.
Results Nineteen of 21 tumours responded promptly to immunocryosurgery; two tumours required additional treatment cycles to clear. Thus, the clinical clearance rate was 100%. Only 1 of 21(5%) tumour relapsed after at least 18 months of follow-up (cumulative efficacy: 95%).
Conclusions 'Immunocryosurgery' is a promising non-surgical combination modality to treat 'high-risk-for-recurrence BCCs'. Initial evidence is suggestive of an at least additive effect of the two combined modalities. Further studies comparing immunocryosurgery directly with cryosurgery and imiquimod monotherapies will confirm the reported results. 相似文献
Methods Thirteen patients with 21 biopsy-proven tumours (4 of 21 relapses after prior surgery) were included. After 2–5 weeks (median, 3) of daily 5% imiquimod cream application, the tumours were treated by liquid N
Results Nineteen of 21 tumours responded promptly to immunocryosurgery; two tumours required additional treatment cycles to clear. Thus, the clinical clearance rate was 100%. Only 1 of 21(5%) tumour relapsed after at least 18 months of follow-up (cumulative efficacy: 95%).
Conclusions 'Immunocryosurgery' is a promising non-surgical combination modality to treat 'high-risk-for-recurrence BCCs'. Initial evidence is suggestive of an at least additive effect of the two combined modalities. Further studies comparing immunocryosurgery directly with cryosurgery and imiquimod monotherapies will confirm the reported results. 相似文献
2.
Effects of hyperglycemia on glucose transporters of the muscle: use of the renal glucose reabsorption inhibitor phlorizin to control glycemia. 总被引:2,自引:0,他引:2
D Dimitrakoudis M Vranic A Klip 《Journal of the American Society of Nephrology : JASN》1992,3(5):1078-1091
Individuals with non-insulin dependent or insulin-dependent diabetes mellitus present insulin resistance in peripheral tissues. This is reflected in a subnormal whole body insulin-dependent glucose utilization, largely dependent on skeletal muscle. Glucose transport across the cell membrane of this tissue is rate limiting in the utilization of the hexose. Therefore, it is possible that a defect exists in insulin-dependent glucose transport in skeletal muscle in diabetic states. This review focuses on two questions: is there a defect at the level of glucose transporters in skeletal muscle of diabetic animal models, and is this a consequence of abnormal insulin or glucose levels? The latter question arises from the fact that these parameters usually vary inversely to each other. Glucose transport into skeletal muscle occurs by two membrane proteins, the GLUT1 and GLUT4 gene products. By subcellular fractionation and Western blotting with isoform-specific antibodies, it was determined that isolated plasma membranes (PM) contain GLUT4 and GLUT1 proteins at a molar ratio of 3.5:1 and that an intracellular fraction (internal membranes; IM) different from sarcoplasmic reticulum contains only GLUT4 transporters. The IM furnishes transporters to the PM in response to insulin. Both transporter isoforms bind cytochalasin B in a D-glucose-protectable fashion. In streptozocin-induced diabetes of the rat with normal fasting insulin levels and marked hyperglycemia, the number of cytochalasin B-binding sites and of GLUT4 proteins diminishes in the PM whereas the GLUT1 proteins increase to a new ratio of about 1.5:1 GLUT4:GLUT1. In the IM, the levels of GLUT4 protein drop, as does the cellular GLUT4 mRNA. To investigate if these changes are associated with hyperglycemia, glucose levels were corrected back to normal values for a 24-h period with sc injections of phlorizin to block proximal tubule glucose reabsorption. This treatment restored cytochalasin B binding, restored GLUT4 and GLUT1 values back to normal levels in the PM, and partly restored cytochalasin B binding but not GLUT4 levels in the IM, consistent with only a partial recovery of GLUT4 mRNA. It is concluded that GLUT4 protein in the PM correlates inversely whereas GLUT1 protein correlates directly with glycemia. It is proposed that the decrease in GLUT4 levels is a protective mechanism, sparing skeletal muscle from gaining glucose and experiencing diabetic complications, albeit at the expense of becoming insulin resistant.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
3.
Mulkerrin EC; Clark BA; Epstein FH 《QJM : monthly journal of the Association of Physicians》1997,90(6):411-415
We studied blood pressure and natriuretic responses to acute salt loading,
and the effect of non-steroidal anti-inflammatory agents on these
responses, in five healthy normotensive women aged 65 to 71 years. Five
women aged 25 to 31 years acted as controls. Intravenous saline loading,
with and without prior ingestion of ibuprofen, was 15 ml/kg/h for 3 h.
Baseline blood pressures were higher in the elderly. Saline infusion
without ibuprofen raised systolic blood pressure (SBP) by about 25 mmHg in
the older group only. Ibuprofen increased baseline SBP in the elderly (129
+/- 6 vs. 116 +/- 5 mmHg, p < 0.05). Saline loading after ibuprofen
again raised blood pressure by about 25 mmHg in the elderly only. The
elderly group showed markedly increased sodium excretion during saline
loading, but this was reduced by ibuprofen. Ibuprofen had no effect on SBP
or sodium excretion in controls. Ageing appears to increase susceptibility
to salt retention and hypertension from non-steroidal anti-inflammatory
agents.
相似文献
4.
Uroscopy in the 21st century: high-field NMR spectroscopy 总被引:1,自引:1,他引:0
Neild GH; Foxall PJ; Lindon JC; Holmes EC; Nicholson JK 《Nephrology, dialysis, transplantation》1997,12(3):404-417
From the experiments described, it can be seen that there are different
research approaches that can be taken and these are summarized in Table 1.
Whereas much scientific research is principally hypothesis led, there
remains, nevertheless, an important place for exploratory research. High
resolution NMR can measure, directly and simultaneously, a wide range of
endogenous metabolites in biological fluids and has the unique capability
of providing structural information on the metabolites detected. It has
proved to be a powerful research tool with which to study inherited
metabolic diseases, renal disease, drug metabolism, and toxicity, and can
be used to monitor the effects of drug therapy. For instance, by using a
library of experimental toxins one can map the metabolic profile of
site-specific nephron injury. With this approach in man one could
eventually take an unknown disease such as Balkan nephropathy and predict
the initial site of tubular injury, the mode of injury and therefore the
kind of toxin capable of producing that injury. NMR spectroscopic
techniques are still advancing rapidly, with ever increasing sensitivity
and sophistication of NMR pulse sequences to enhance structural elucidation
in complex mixtures. Given the advances in directly coupled HPLC-NMR and
even HPLC-NMR-mass spectroscopy it is likely that these technologies in
conjunction with pattern recognition will make major contribution to our
understanding of renal processes and provide new diagnostic insights in the
21st century.
相似文献
5.
Spinocerebellar ataxia type 7 (SCA7): a neurodegenerative disorder with neuronal intranuclear inclusions 总被引:8,自引:13,他引:8
Holmberg M; Duyckaerts C; Durr A; Cancel G; Gourfinkel-An I; Damier P; Faucheux B; Trottier Y; Hirsch EC; Agid Y; Brice A 《Human molecular genetics》1998,7(5):913-918
Autosomal dominant cerebellar ataxia with progressive macular degeneration
is caused by a CAG/glutamine repeat expansion in the SCA7 gene/protein.
Neuronal intranuclear inclusions were detected in the brain of an early
onset SCA7 case with the 1C2 antibody directed against an expanded
polyglutamine domain. Nuclear inclusions were most frequent in the inferior
olivary complex, a site of severe neuronal loss in SCA7. They were also
observed in other brain regions, including the cerebral cortex, not
considered to be affected in the disease. Using confocal microscopy we
showed that some inclusions were ubiquitinated, but to varying degrees,
ranging from <1% in the cerebral cortex to 60% in the inferior olive. In
addition, we also observed cytoplasmic staining using the 1C2 antibody,
particularly in the supramarginal gyrus, the hippocampus, the thalamus, the
lateral geniculate body and the pontine nuclei. These data confirm that the
presence of intranuclear inclusions in neurons is a common characteristic
of disorders caused by CAG/polyglutamine expansions, but unlike what has
been reported for Huntington's disease, SCA1 and SCA3/MJD, in SCA7 the
inclusions were not restricted to the sites of severe neuronal loss.
相似文献
6.
Exercise- and insulin-stimulated muscle glucose transport: distinct mechanisms of regulation. 总被引:2,自引:0,他引:2
In mammals, skeletal muscle is the primary target for the stimulation of glucose transport by a variety of activators. These include the hormone insulin and stimuli which increase energy demand such as exercise, hypoxia, and challenges to the oxidative chain. While it is known that both stimuli rapidly elevate glucose uptake into muscle by signalling the translocation of glucose transporters from intracellular stores to the plasma membrane, there are numerous contrasts between energy stressors and insulin in their mechanisms of glucose transport activation. Exercise and insulin recruit distinct intracellular pools of glucose transporters in skeletal muscle and the maximal effects of contraction and insulin are additive. Activation of phosphatidylinositol 3-kinase (PI3-K) is utilized by insulin to induce glucose transporter translocation, but does not participate in the responses to exercise or hypoxia. These findings suggest that energy stressors utilize different mechanisms from insulin to increase glucose influx; however, how these factors elicit their response is not clear. This review will summarize our current knowledge of these alternative pathways of glucose transport regulation. Emphasis is placed on the use of the mitochondrial uncoupler dinitrophenol to investigate mediators of this alternative signalling pathway in L6 muscle cells, a line used to characterize physiological responses in muscle such as glucose transport. 相似文献
7.
Initial validation of the SLEEP-50 questionnaire 总被引:1,自引:0,他引:1
Initial psychometric properties of the SLEEP-50 questionnaire, designed to detect sleep disorders as listed in the Diagnostic and Statistical Manual of Mental Disorders (4th ed., Text Revision), were examined. The sample consisted of 377 college students, 246 sleep patients, 32 nightmare sufferers, and 44 healthy volunteers. The internal consistency was high (Cronbach's alpha = .85); test-retest correlations fell between .65 and .89. Principal component analysis with a direct oblimin rotation revealed a factor structure that closely matched the designed structure. Sensitivity and specificity scores were promising for all sleep disorders; the agreement between all clinical diagnoses and SLEEP-50-classifications was substantial (kappa = .77). These initial findings indicate that the SLEEP-50 seems able to detect a variety of sleep disorders. The SLEEP-50 can aid in screening for common sleep disorders in the general population. 相似文献
8.
I. B. M. van der Fits A. W. J. Klip L. A. van Eykern M. Hadders-Algra 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1998,120(2):202-216
The present study evaluated the effect of different positions, which varied in the amount of bodily support, on postural control
during fast pointing movements. Fourteen adult subjects were studied in standing, various sitting and lying positions. Multiple
surface electromyograms (EMGs) of arm, neck, trunk and upper leg muscles and kinematics were recorded during a standard series
of unilateral arm movements. Two additional series, consisting of bilateral arm movements and unilateral arm movements with
an additional weight, were performed to assess whether additional task-load affected postural adjustments differently in a
sitting and standing position. Two pointing strategies were used – despite identical instructions. Seven subjects showed an
elbow extension throughout the movements. They used the deltoid (DE) as the prime mover (DE group). The other seven subjects
performed the movement with a slight elbow flexion and used the biceps brachii (BB) as the prime mover (BB group). The two
strategies had a differential effect on the postural adjustments: postural activity was less and substantially later in the
BB-group than in the DE group. Anticipatory postural muscle activity was only present in the DE group during stance. In all
positions and task-load conditions the dorsal postural muscles were activated before their ventral antagonists. The activation
rate, the timing and – to a lesser extent – the amplitude of the dorsal muscle activity was position dependent. The position
dependency was mainly found in the caudally located lumbar extensor (LE) and hamstrings (HAM) muscles. The EMG amplitude of
LE and HAM was also affected by body geometry (trunk and pelvis position). Position and body geometry had only a minor effect
on the activity of the neck and thoracic extensor muscles. This difference in behaviour of lower and upper postural muscles
suggests that they could serve different postural tasks: the lower muscles being more involved in keeping the centre of mass
within the limits of the support surface, and the upper ones in counteracting the reaction forces generated by movement onset.
Increasing task-load by performing bilateral movements and – to a minor extent – during loaded unilateral movements affected
the temporal and quantitative characteristics of the postural adjustments during standing and sitting in a similar way. The
effect was present mainly during the early part of the response (within 100 ms after prime mover onset). This suggests that
feedforward or anticipatory mechanisms play a major role in the task-specific modulation of postural adjustments.
Received: 9 April 1997 / Accepted: 9 October 1997 相似文献
9.
An increased cellular Ca2+ content has been associated with Duchenne muscular dystrophy (DMD). However, estimates of the free cytoplasmic Ca2+ concentration ([Ca2+]i) in cells of DMD patients were not available. We compared the [Ca2+]i levels of normal and DMD peripheral blood lymphocytes and Epstein-Barr virus-transformed lymphoblasts using the novel probe, quin 2, an internally trapped fluorescent indicator. The [Ca2+]i levels of normal and DMD cells were not significantly different. 相似文献
10.
VS Khoo KH Liew EC Crennan IM D'Costa G Quong 《Journal of Medical Imaging and Radiation Oncology》1998,42(1):52-57
Thyroid dysfunction can develop in patients with Hodgkin's disease who are treated with mantle irradiation. During the period 1970-89, the records of 320 patients who received mantle irradiation and who had thyroid function tests (TFT) were retrospectively reviewed. The median age was 30 years (range, 7-69 years). The median mantle and thyroid dose was 36 Gy (range, 30-40 Gy) and 39.8 Gy (range, 32-65 Gy), respectively. Overall thyroid dysfunction was present in 39% of the patients. Clinical hypothyroidism was seen in 10% and biochemical hypothyroidism was noted in 25%. Hyperthyroidism was found in 4% of patients. Thyroid nodules had developed in six patients (2%), of which those in four patients were malignant. Age, sex, histological subtype, stage of disease, dose, lymphangiogram and treatment with chemotherapy were not significant factors in the development of thyroid dysfunction. The narrow dose range prevented adequate analysis of dose effect. The results indicate that the incidence of thyroid abnormalities is high enough to warrant regular TFT assessment with pre-irradiation levels and follow-up testing for life because the development of abnormalities can occur many years later. Thyroid examination should form part of the routine follow-up examination and any abnormality should be promptly investigated. 相似文献