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21.
Amplification or duplication of the AML1 gene at chromosome band 21q22 was detected by FISH using a locus-specific probe in three out of 171 unselected patients with therapy-related myelodysplasia (t-MDS) or t-AML (1.7%). In two patients AML1 signals were located tandemly on derivative chromosomes, in one patient on a dic(9;21) and in the the other patient on a derivative chromosome 18 made up of interchanging layers of material from chromosomes 9, 14, 18, and 21. In the third patient three single supernumerary copies of AML1 were located on derivatives of chromosomes 19 and 21. All three patients were older, had previously received therapy with alkylating agents without topoisomerase II inhibitors, had complex karyotypes including abnormalities of chromosomes 5 or 7, and presented acquired point mutations of the TP53 gene. No point mutations of the AML1 gene were observed. The results support a pivotal role of impaired TP53 function in the development of gene amplification or duplication in t-MDS and t-AML. 相似文献
22.
Computer simulation can be used to integrate existing toxicity information within a biologically realistic framework. Simulation models calculate relevant measures of target tissue dose based on physiological, biochemical and physicochemical properties and readily support the dose, route, species and interchemical extrapolations necessary for human risk assessment. Because these models require very specific information, much of which can be obtained in vitro, they are much less dependent on extensive animal experiments than conventional risk assessment methods. With continuing development, simulation modeling will become an invaluable tool for improving experimental designs, for interpreting animal toxicity tests, and for estimating the importance of the animal toxicity observations for people. 相似文献
23.
Campylobacter pyloridis in peptic ulcer disease. I. Gastric and duodenal infection caused by C. pyloridis: histopathologic and microbiologic findings 总被引:14,自引:0,他引:14
L P Andersen S Holck C O Povlsen L Elsborg T Justesen 《Scandinavian journal of gastroenterology》1987,22(2):219-224
In this study 153 patients with dyspepsia were biopsied in the gastric antrum and duodenum. All specimens were investigated histopathologically and microbiologically for the presence of Campylobacter pyloridis, and the type of inflammation was recorded in accordance with Morson's criteria. C. pyloridis was found beneath the mucus close to the epithelial cells and mostly in connection with granulocytic infiltration (active gastritis). C. pyloridis was cultured from all of 10 patients with histologically active gastritis and active duodenitis, in 86% of 64 patients with active gastritis and morphologically normal duodenum, and in only 5% of 79 patients without morphologic gastric and duodenal changes. The close relation between active gastritis and C. pyloridis shows that C. pyloridis plays an important role in gastric inflammation, as it fulfils the criterion for a localized bacterial infection. 相似文献
24.
Abstract Laser Doppler flowmetry (LDF) was used to study the changes in pulpal blood flow (PBF) evoked by application of cold or heat to the palatinal surfaces of teeth 11 or 21 in nine young subjects. Switching from a thermode temperature of 33° to 5° G on average induced a slow decrease of PBF to about 80% of control, and also warming to 39°C evoked a small reduction in most subjects. Inter individual differences were large, however, and both cooling and warming sometimes triggered a rise in PBF. In contrast, skin blood flow, as recorded with LDF in the forearm, invariably rose during warming and fell during local cooling. The results suggested a more complex interaction between local and nervously mediated effects of moderate changes in temperature in the tooth pulp than skin, and that the previous held view of cold and heat decreasing and increasing PBF, respectively, is wrong. 相似文献
25.
A. Aamodt J. Lund-Larsen J. Eine E. Andersen P. Benum O. Schnell Husby 《Journal of orthopaedic research》1997,15(6):927-931
Two conflicting theories exist concerning the stress pattern for the proximal lateral aspect of the human femur. According to the classic theory of Pauwels, a bending moment on the femur leads to compression medially and to tension laterally. The alternative theory is that muscle forces contribute to a moment-free loading of the femur, with both the medial and lateral cortices subjected to compression. To examine these theories, we measured the strain at the external surface of the proximal lateral aspect of the femur of two female patients undergoing surgery for “snapping hip syndrome.” During the surgical procedure, a strain-gauge rosette was bonded to the lateral aspect of the femur and the cortical strains were monitored while the patient performed a series of activities. In both patients, principle tensile strain increased significantly during one-legged stance, walking, and stair climbing as compared with that during two-legged stance. During each loading situation, the principal tensile strain was aligned within 22° to the longitudinal femoral axis. Dynamic strain measurements consistently revealed tensile axial strain at the lateral aspect of the femur during each activity. The present studv supports the classic bending theory of Pauwels and demonstrates that the proximal lateral aspect of the femur is subjected to tension during the stance phase of gait. 相似文献
26.
27.
E. Brodtkorb T. Torbergsen K. O. Nakken K. Andersen R. Gimse O. Sjaastad 《Acta neurologica Scandinavica》1994,90(4):232-240
Introduction – Arthrogryposis multiplex congenita (AMC) may be associated with multiple developmental defects. In some severely affected newborns with AMC, autopsy studies have suggested a common mechanism of malmigration at the spinal and cerebral levels. To our knowledge, a constellation of arthrogryposis, epileptic seizures, and brain migrational anomalies in adult patients has not previously been described in a clinical material. Material and methods – Six consecutive adult patients with arthrogryposis multiplex congenita and epileptic seizures form the basis of the present study. Five patients had joint contractures and reduced muscle volume restricted to the lower extremities, whereas one patient had predominantly upper extremity affection. They were studied with magnetic resonance imaging (MRI), EEG, EMG, a neuropsychological test battery, and chromosome analysis. Results – Four of them had clear evidence of migrational brain disorders, demonstrated by MRI, in three of them roughly corresponding to the focal epileptiform EEG activity. Five of the patients had partial seizures, whereas one only had generalized tonic-clonic seizures. The MRI findings included polymicrogyria, pachygyria, and fused schizencephaly. Four had neurogenic EMG changes, one had myopathic EMG features, and one had an unremarkable EMG pattern in affected muscles. All patients witL demonstrable migrational disorders showed abnormal neuropsychological features. Three patients were mentally retarded. A chromosome abnormality in the form of a ring chromosome 18 was present in one patient. Conclusion – We suggest that AMC, epileptic seizures, and migrational brain disorders may form the integral parts of a hitherto undescribed syndrome in adults. A wide-spread defect in neuronal migration along the entire neural axis may be the underlying mechanism of the cerebral and the peripheral symptoms. 相似文献
28.
P. M. Patel C. L. Flemming S. J. Russell I. A. McKay K. A. MacLennan G. M. Box S. A. Eccles M. K. Collins 《British journal of cancer》1993,68(2):295-302
Engineering of a variety of rodent tumour cells to secrete either interleukin 2 (IL-2), or interleukin 4 (IL-4), has been demonstrated to reduce their tumorigenicity. However the mechanisms of action of secreted IL-2 and IL-4 have not been compared in a single rodent tumour. Here we demonstrate that the weakly immunogenic murine fibrosarcoma FS29 had reduced growth rate and in some cases was rejected by syngeneic animals, when modified to secrete either IL-2 or IL-4, but not IL-5. Immunohistochemical analysis of tumour nodules undergoing regression showed stimulation of a largely lymphocytic infiltrate by IL-2 and a macrophage and granulocyte infiltrate, with a small number of lymphocytes by IL-4. Indeed, secretion of low levels of IL-2 and IL-4 in combination resulted in optimal rejection, suggesting that the two cytokines might mobilise different and complementary effector cell mechanisms. Both IL-2 and IL-4-secreting cells failed to induce the rejection of admixed, unmodified FS29 cells. The loss of cytokine secreting cells from such admixtures occurred more rapidly for IL-2-secreting cells. Injection of IL-4-secreting, but not IL-2-secreting FS29 cells could protect mice from a delayed challenge with unmodified FS29 cells. These data suggest that IL-4 secretion stimulates the better long-term host anti-tumour response. 相似文献
29.
The retention of [99mTc]-d,l-HM-PAO in the human brain after intracarotid bolus injection: a kinetic analysis 总被引:1,自引:0,他引:1
N A Lassen A R Andersen L Friberg O B Paulson 《Journal of cerebral blood flow and metabolism》1988,8(6):S13-S22
[99mTc]-d,l-HM-PAO (HM-PAO) was injected rapidly into the internal carotid artery and its retention in the brain was recorded by external scintillation cameras in eight human subjects. A model is described based on three compartments: the lipophilic tracer in the blood pool of the brain, the lipophilic tracer inside the brain, and the hydrophilic form retained in the brain. The retention curve initially drops abruptly, corresponding to the nonextracted fraction of the injectate leaving the brain; it then falls exponentially towards the asymptotic level of the fractional steady-state retention R. Cerebral blood flow (F) was measured using the xenon-133 intracarotid injection method. The first-pass extraction E of HM-PAO was calculated from F using an empiric regression equation. The residue curves for the whole brain after intracarotid HM-PAO injection were analyzed to yield a retention fraction (R') and the brain clearance backflux constant of lipophilic HM-PAO (k). From the kinetic model and the measured values of R', k, and F, the following parameter values could be calculated: the average retained fraction of all tracer supplied to the brain, R = 0.38 +/- 0.05 (mean +/- SD), the conversion rate constant (lipophilic to hydrophilic tracer) in the brain k3 = 0.80 +/- 0.12 min-1, the efflux rate constant (brain to blood) k2 = 0.69 +/- 0.11 min-1, the conversion/clearance ratio alpha = k3/k2 = 1.18 +/- 0.25, the influx (blood clearance) constant K1 = 0.45 +/- 0.11 ml/g/min, and the brain/blood partition ratio lambda = K1/k2 = 0.67 +/- 0.23 ml/g. Using the kinetic model and assuming constancy of alpha, an algorithm was developed that corrects for the blood flow dependent backflux of HM-PAO and results in a more linear relation between regional cerebral blood flow (rCBF) and HM-PAO distribution. 相似文献
30.