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31.
The proportion of diagnosed depressives prescribed antidepressants has increased markedly over the last 20 years, mainly following the introduction of the selective serotonin reuptake inhibitors. However, currently available antidepressants have notable limitations, relating to their only moderate efficacy relative to placebo, relatively slow onset of action, possible withdrawal symptoms, and problems of compliance. Sleep disturbances are often used to identify newly presenting depressive patients, and may be part of a more general alteration of bodily rhythms. There are links between pharmacological treatments and circadian rhythms in depression, which might represent another, new option for the development of a therapeutic approach to depression treatment. Many antidepressants affect sleep, some are sedative, and others have been used specifically in severely insomniac depressives. Disturbances in circadian rhythms may be an integral part of depressive mechanisms, and normalising them via an innovative mechanism of antidepressant action may be a fruitful avenue in the search for improved antidepressant agents. 相似文献
32.
Pawan Kumar Dhruva Rao Deborah Clements Michael M. Davies Jared Torkington 《Surgical endoscopy》2007,21(6):1036
We present our comments on the above article. 相似文献
33.
Free radical mechanisms in relation to tissue injury 总被引:4,自引:0,他引:4
34.
Pamela H. Orr Victor Dong Marlis L. Schroeder Malcolm R. Ogborn 《Pediatric nephrology (Berlin, Germany)》1995,9(5):612-613
P1 blood group positivity has been postulated as a host factor which may provide protection against the development of post-enteropathic hemolytic uremic syndrome (HUS). In this study, blood group status in 20 Inuit survivors ofEscherichia coli 0157: H7-associated HUS was compared with age-and sex-matched controls from the same community who had experienced uncomplicated diarrheal illness due to the same pathogen. Of 20 HUS survivors, 6 were P1 antigen positive compared with 8 of the 20 controls (P=0.7). We conclude that P1 antigen positivity was not protective against HUS in this population. Further studies of this condition to clarify the role of host factors in verotoxin-induced endothelial damage are indicated. 相似文献
35.
36.
Long Fibre Growth by Axons of Embryonic Mouse Hippocampal Neurons Microtransplanted into the Adult Rat Fimbria 总被引:1,自引:0,他引:1
We have described a method for the microtransplantation of a suspension of a few thousand cells from mid to late embryonic mouse hippocampi into the fimbria of immunosuppressed adult rat hosts. There was close graft-to-host contact, across a non-scarred interface. The transplanted cells included CA3 type pyramids, and were enclosed within the host myelinated fibre tract, whose glial framework was largely undisturbed. Immunohistochemistry of two species-specific markers (M6 and Thy-1.2) showed that the donor mouse neurons grew fine (<0.5 μm diameter) axons which extended singly or in fascicles through the rat host fimbria for a maximum distance of at least 10 mm. The donor axons were intimately integrated among and closely aligned to the host tract axons and to the interfascicular glial rows of the host tract. The axons travelled (i) laterally through the ipsilateral fimbria, (ii) medially across the midline in the ventral hippocampal commissure to reach the contralateral fimbria and alveus, and (iii) rostro-medially to the septum. On approaching the terminal fields appropriate to hippocampal CA3 pyramidal cell axons, the transplant axons gave rise to fine preterminal branches which were continuous with a reticular or amorphous immunoreactivity in the stratum oriens and stratum pyramidale of the ipsilateral hippocampus, and in the lateral and triangular septal nuclei. The donor axons extended along the host fimbria at a rate of ∼ 1 mm per day, reaching their terminal field destinations by ∼1–2 weeks. At 7 weeks the projections were maintained, but with little further extension. These observations indicate that the microenvironment of myelinated adult fibre tracts is permissive for an abundant and rapid growth of axons from transplanted embryonic cell suspensions. These axons can leave host tracts to invade appropriate terminal fields. 相似文献
37.
The cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice 总被引:2,自引:0,他引:2
C. P. Clifford D. A. Adams S. Murray G. W. Taylor M. R. Wilkins A. R. Boobis D. S. Davies 《European journal of clinical pharmacology》1997,52(4):311-315
Objective: To determine whether the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine are affected by the concomitant
administration of grapefruit juice.
Methods: Six healthy volunteers were recruited for a balanced cross-over study. Each volunteer received 120 mg terfenadine 30 min
after drinking 300 ml of either water or freshly squeezed grapefruit juice. The alternative treatment was administered on
the second study day 2 weeks later. Measurements of the area under the terfenadine plasma concentration-time curve (AUC),
maximum terfenadine concentration (Cmax) and the time to maximum concentration (tmax) were made, and the corrected QT (QTc) interval was measured from the surface electrocardiogram.
Results: Terfenadine was quantifiable in plasma in all 6 subjects on both study days for up to 24 h post-dosing. The AUC of terfenadine
was significantly increased by concomitant grapefruit administration (median values 40.6 vs 16.3 ng · ml−1 · h), as was the Cmax (median values 7.2 vs 2.1 ng · ml−1). The tmax was not significantly increased and there was no significant change in the median QTc interval despite the increased terfenadine
levels. The 95% confidence interval for the difference in the change in QTc interval at Cmax was −13 to +38 ms.
Conclusion: Administration of grapefruit juice concomitantly with terfenadine may lead to an increase in terfenadine bioavailability,
but the increase observed in this study did not lead to significant cardiotoxicity in normal subjects. However, this does
not exclude the risk of cardiotoxicity in high-risk subjects given greater doses of grapefruit juice over longer periods of
time.
Received: 14 October 1996 / Accepted in revised form: 10 December 1996 相似文献
38.
Assessment of the severity of coronary artery disease at postmortem examination. Are the measurements clinically valid? 总被引:2,自引:2,他引:0
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OBJECTIVE--To compare the assessment of severity of coronary artery stenosis by the conventional pathology methods with a method designed to resemble quantitative angiography. DESIGN--31 human hearts harvested at necropsy were fixed by perfusion of the aortic root with 10% formol saline at 120 mm Hg for 24 hours. The right coronary and left anterior descending coronary arteries were transversely sliced every 2 mm and the absolute lumen dimensions plotted against the distance from the coronary ostium. Stenosis figures were calculated by comparing the lumen diameter with the lumen diameters in adjacent normal arterial segments in a manner identical to that used in angiographic measurement. The coronary artery segments were then processed histologically. Stenosis was then remeasured by comparing the lumen diameter with the diameter of the vessel within the internal elastic lamina identified by elastic van Gieson staining. RESULTS--Compared with the method that was analogous to angiography, the pathology method used on histological slides overestimated the degree of stenosis by 25-30%. The lack of concordance between the methods was not a function of the severity of the stenosis. CONCLUSION--When they read necropsy reports in which the severity of coronary artery stenosis is assessed cardiologists should be aware of the discrepancy between clinical and pathological methods. 相似文献
39.
G. M. Halliday L. Davies D. A. McRitchie H. Cartwright R. Pamphlett J. G. L. Morris 《Acta neuropathologica》1995,90(1):68-75
A 66-year-old woman presented with an alien limb syndrome without dementia. The course of her illness was unremitting and at autopsy 6 years later her diagnosis was confirmed as corticobasal degeneration without Alzheimer-type pathology. Although the presence of ballooned achromatic cortical neurons and cell loss from the substantia nigra distinguishes such patients, the site and density of achromatic neurons has not previously been quantified. We show that immunohistochemistry for the cell stress protein ubiquitin selectively stains these achromatic neurons, whereas they do not stain for abnormally phosphorylated tau protein. Phosphorylated neurofilament antibodies recognise both ballooned and non-ballooned neurons. In this case, high densities of ubiquitin-positive ballooned neurons were found in frontal cortical regions with the highest densities in layers V and VI of the anterior cingulate cortex. In addition, high densities of ubiquitin-positive ballooned neurons were found in the insular cortex, claustrum and amygdala. These results confirm past reports of frontal pathology, but show that there is also considerable pathology in insular and parahippocampal cortical regions and some subcortical regions. Our findings suggest that the distribution and staining characteristics of ballooned neurons in corticobasal degeneration may help to differentiate these cases pathologically, while the absence of dementia appears to be an important clinical criterion. 相似文献
40.