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61.
The diverse physiological effects of sphingosine 1-phosphate (S1P) are mostly mediated by its five cognate G protein-coupled receptors, S1P1-S1P5, which have attracted much attention as future drug targets. To gain insight into S1P2-mediated signaling, we analyzed frequent spontaneous seizures in S1P2-deficient (S1P2−/−) mice obtained after several backcrosses onto a C57BL/6N background. Full-time video recording of 120 S1P2−/− mice identified 420 seizures both day and night between postnatal days 25 and 45, which were accompanied by high-voltage synchronized cortical discharges and a series of typical episodes: wild run, tonic-clonic convulsion, freezing, and, occasionally, death. Nearly 40% of 224 S1P2−/− mice died after such seizures, while the remaining 60% of the mice survived to adulthood; however, approximately half of the deliveries from S1P2−/− pregnant mice resulted in neonatal death. In situ hybridization revealed exclusive s1p2 expression in the hippocampal pyramidal/granular neurons of wild-type mice, and immunohistochemistry/microarray analyses identified enhanced gliosis in the whole hippocampus and its neighboring neocortex in seizure-prone adult S1P2−/− mice. Seizure-prone adult S1P2−/− mice displayed impaired spatial working memory in the eight-arm radial maze test and increased anxiety in the elevated plus maze test, whereas their passive avoidance learning memory performance in the step-through test and hippocampal long-term potentiation was indistinguishable from that of wild-type mice. Our findings suggest that blockade of S1P2 signaling may cause seizures/hippocampal insults and impair some specific central nervous system functions.  相似文献   
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63.
OBJECTIVE: To study the after-effect of transcranial direct current stimulation (tDCS) over the sensorimotor cortex on the size of somatosensory evoked potentials (SEPs) in humans. METHODS: SEPs were elicited by electrical stimulation of right or left median nerve at the wrist before and after anodal or cathodal tDCS in 8 healthy subjects. tDCS was applied for 10 min to the left motor cortex at a current strength of 1 mA. RESULTS: Amplitudes of P25/N33, N33/P40 (parietal components) and P22/N30 (frontal component) following right median nerve stimulation were significantly increased for at least 60 min after the end of anodal tDCS, whereas P14/N20, N20/P25 (parietal components) and N18/P22 (frontal component) were unaffected. There was no effect on SEPs evoked by left median nerve stimulation. Cathodal tDCS had no effect on SEPs evoked from stimulation of either arm. CONCLUSIONS: Anodal tDCS over the sensorimotor cortex can induce a long-lasting increase in the size of ipsilateral cortical components of SEPs. SIGNIFICANCE: tDCS can modulate cortical somatosensory processing in humans and might be a useful tool to induce plasticity in cortical sensory processing.  相似文献   
64.
Neurofibrillary tangles (NFT) in Alzheimer's disease (AD) are composed of abnormally phosphorylated tau proteins. Many phosphorylation sites have been reported in the AD brain, and NFT distribution was now roughly classified into 3 stages by Braak stage; this classification is based on pathological studies using the specific silver impregnation technique. The aim of our study was to examine the regional distribution of differently phosphorylated tau proteins with 5 site-specific monoclonal antibodies against the tau proteins, AT8, AT180, HT7, Tau2 and Tau5. We then compared our findings with those obtained from silver-stained NFT in an attempt to clarify the relationship between abnormal phosphorylation sites of the tau protein and NFT development. AT180 and AT8 labeled the highest and Tau2 the lowest density of NFT in any regions, while Tau5 and HT7 showed inconsistent distribution. In the limbic cortex, cornu ammonis, entorhinal cortex and cingulate cortex, silver-stained NFT density significantly correlated with density of NFT labeled with the 5 anti-tau antibodies, but cerebral isocortices showed heterogenous patterns of tau-positive NFT. Quantification of tau-positive regional NFT density showed that the AD-associated phosphorylation process progresses from the C-terminal to the N-terminal of the amino acid sequence, and correlation of Gallyas-stained NFT density with tau-labeled NFT density was more significant in the limbic cortices than the cerebral isocortices, which implies that stereotypical phosphorylation occurs in the limbic structures.  相似文献   
65.
Synaptic inhibition from the substantia nigra pars reticulata (SNr) to the mesencephalic dopaminergic neurons, which was mediated by gamma (gamma)-amino-butyric acid (GABA), was investigated in a midbrain slice preparation of Wistar rats. Whole-cell patch-clamp recordings were used to record synaptic potentials/currents from the dopaminergic neurons (n = 93) located in the retrorubral field (n = 22), the substantia nigra pars compacta (n = 47) and the ventral tegmental area (n = 24). In the presence of ionotropic glutamate receptor antagonists electrical stimulation of the SNr induced inhibitory postsynaptic potentials (IPSPs) and/or currents (IPSCs) in 83 neurons. The IPSPs/IPSCs were comprised early and late components. The early IPSPs/IPSCs were mediated by chloride currents through GABA(A) receptors. The late IPSPs/IPSCs were mediated by potassium currents through GABA(B) receptors. Both GABA(A)- and GABA(B)-IPSPs were amplified by repetitive stimuli with frequencies between 25 and 200 Hz. This frequency range covers the firing frequencies of SNr neurons in vivo. It was observed that an application of a GABA(B) receptor antagonist increased the amplitude of the GABA(A)-IPSPs. The amplification was followed by a rebound depolarization that induced transient firing of dopaminergic neurons. These properties of the IPSPs were common in all of the three dopaminergic nuclei. These results suggest that postsynaptic GABA(A)- and GABA(B)-inhibition contribute to transient and persistent alternations of the excitability of dopaminergic neurons, respectively. These postsynaptic mechanisms may be, in turn, regulated by presynaptic GABA(B)-inhibition. Nigral GABAergic input may provide the temporospatial regulation of the background excitability of mesencephalic dopaminergic systems.  相似文献   
66.
An umbilical cyst originating from an omphalomesenteric duct remnant is extremely rare, and to the best of our knowledge, it has scarcely been reported in medical literature. We present ultrasonographic manifestations and computed tomographic findings of an umbilical cyst originating from an omphalomesenteric duct remnant in a 6-year-old girl. In cases of umbilical cyst, radiographic evaluation alone may not differentiate an omphalomesenteric duct remnant with heterotopic gastric mucosa from a urachal remnant, and surgical intervention is required.  相似文献   
67.
We used functional magnetic resonance imaging (fMRI) to investigate whether activation in Broca's area is greater during the processing of passive versus active sentences in the brains of healthy subjects. Twenty Japanese native speakers performed a visual sentence comprehension task in which they were asked to read a visually presented sentence and to identify the agent or the patient in the sentence by pressing a button. We found that the processing of passive sentences elicited no greater activation than that of active sentences in Broca's area. However, passive sentences elicited greater activation than active sentences in the left frontal operculum and the inferior parietal lobule. Thus, our neuroimaging results suggest that deficits in the comprehension of passive sentences in Japanese aphasics are induced not by lesions to Broca's area, but to the left frontal operculum and/or the inferior parietal lobule.  相似文献   
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69.
We report a 57‐year‐old patient with Creutzfeldt‐Jakob disease that initially presented with right parietal lobe syndrome. He featured early dystonic and hemiparetic posture of the left upper limb, finger agnosia, geographic disorientation and acalculia and developed myoclonus from the left upper extremity and right‐sided periodic synchronized discharges. He died 2 years and 3 months later. Brain autopsy revealed a marked reduction in brain weight, extensive cortical spongiform changes and white matter degeneration. Immunolabeled prion proteins were deposited diffusely in the neuropil. Accentuation of the cortical change was unclear but white matter degeneration was more severe in the right parietal lobe than in the left parietal lobe. Right parietal lobe syndrome is rarely reported as an initial symptom of Creutzfeldt‐Jakob disease and can be a clinical variant of the disease.  相似文献   
70.
A case of xeroderma pigmentosum (XP) group D in a 39‐year‐old Japanese man is reported. The patient had suffered from moderate to severe solar sensitivity and freckle‐like pigmented macules in sun‐exposed areas since 6 years of age, and developed skin malignancies such as squamous cell carcinoma, actinic keratosis, Bowen’s disease and basal cell carcinoma. The minimal erythema dose for ultraviolet (UV) radiation was decreased with a delayed peak reaction. The level of unscheduled DNA synthesis of fibroblasts from the patient was 70% of normal, while they expressed POLH, a gene product responsible for the XP variant. Whole‐exome sequencing indicated that the patient harbored a homozygous mutation of c.1802G>T, p.Arg601Leu in ERCC2. A genetic complementation test was carried out by host cell reactivation assay, which showed that the patient’s fibroblasts recovered only when they were transfected with XPD cDNA, confirming the diagnosis of XP‐D. Arg601Leu mutation in ERCC2 may be related to mild UV radiation sensitivity and moderate skin lesions.  相似文献   
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