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51.
Indices of blood oxygen transport (hemoglobin-oxygen affinity, pCO2, pH, pO2, etc.) and prooxidant-antioxidant state (Schiff bases, conjugated dienes, catalase, retinal, alpha-tocopherol) were measured in rabbit blood and the liver during postischemic reperfusion. Hepatic ischemia was induced for 30 min by ligation of a hepatica propria, and reperfusion lasted for 120 min. Hepatic ischemia worsened blood oxygen transport. Restoration of arterial blood flow did not result in improvement of oxygen delivery. Moreover, marked metabolic acidosis was observed throughout 2 hr of reperfusion. Ischemia induced a shift of oxyhemoglobin dissociation curve to the right. This shift persisted after restoration of hepatic arterial blood flow facilitating increased oxygen transport to tissues. Changes in blood oxygen transport during hepatic ischemia/reperfusion were accompanied with high activity of free radical processes. During reperfusion, the largest increase in content of lipid peroxidation products and the greatest fall of some antioxidant levels except catalase were observed indicating impairment of liver prooxidant-antioxidant balance. The results showed that activation of lipid peroxidation and a decrease in some antioxidant levels during hepatic reperfusion were associated with lowering of hemoglobin-oxygen affinity and suggest participation of the latter in impairment of prooxidant-antioxidant balance.  相似文献   
52.

Background

Myositis is a heterogeneous group of muscular auto-immune diseases with clinical and pathological criteria that allow the classification of patients into different sub-groups. Inclusion body myositis is the most frequent myositis above fifty years of age. Diagnosing inclusion body myositis requires expertise and is challenging. Little is known concerning the pathogenic mechanisms of this disease in which conventional suppressive-immune therapies are inefficacious.

Objectives

Our aim was to deepen our understanding of the immune mechanisms involved in inclusion body myositis and identify specific biomarkers.

Methods

Using a panel of thirty-six markers and mass cytometry, we performed deep immune profiling of peripheral blood cells from inclusion body myositis patients and healthy donors, divided into two cohorts: test and validation cohorts. Potential biomarkers were compared to myositis controls (anti-Jo1-, anti-3-hydroxyl-3-methylglutaryl CoA reductase-, and anti-signal recognition particle-positive patients).

Results

Unsupervised analyses revealed substantial changes only within CD8+ cells. We observed an increase in the frequency of CD8+ cells that expressed high levels of T-bet, and containing mainly both effector and terminally differentiated memory cells. The senescent marker CD57 was overexpressed in CD8+T-bet+ cells of inclusion body myositis patients. As expected, senescent CD8+T-bet+ CD57+ cells of both patients and healthy donors were CD28nullCD27nullCD127null. Surprisingly, non-senescent CD8+T-bet+ CD57- cells in inclusion body myositis patients expressed lower levels of CD28, CD27, and CD127, and expressed higher levels of CD38 and HLA-DR compared to healthy donors. Using classification and regression trees alongside receiver operating characteristics curves, we identified and validated a frequency of CD8+T-bet+ cells >51.5% as a diagnostic biomarker specific to inclusion body myositis, compared to myositis control patients, with a sensitivity of 94.4%, a specificity of 88.5%, and an area under the curve of 0.97.

Conclusion

Using a panel of thirty-six markers by mass cytometry, we identify an activated cell population (CD8+T-bet+ CD57- CD28lowCD27lowCD127low CD38+ HLA-DR+) which could play a role in the physiopathology of inclusion body myositis, and identify CD8+T-bet+ cells as a predominant biomarker of this disease.  相似文献   
53.
 Madin Darby canine kidney cells transformed by alkaline stress (MDCK-F cells) constitutively migrate at a rate of about 1 μm·min–1. Migration depends on the intermittent activity of a Ca2+-stimulated, 53-pS K+ channel (KCa channel) that is inhibitable by charybdotoxin. In the present study we examined whether this intermittent KCa channel activity results in a significant K+ loss across the plasma membrane. K+ efflux from MDCK-F cells should result in a transient increase of extracellular K+ ([K+]e) in the close vicinity of a migrating cell. However, due to the rapid diffusion of K+ ions into the virtually infinite extracellular space, such a transient increase in [K+]e was too small to be detected by conventional K+-selective electrodes. Therefore, we developed a ”shielded ion-sensitive microelectrode” (SIM) that limited diffusion to a small compartment, formed by a shielding pipette which surrounded the tip of the K+-sensitive microelectrode. The SIM improved the signal to noise ratio by a factor of at least three, thus transient increases of [K+]e in the vicinity of MDCK-F cells became detectable. They occurred at a rate of 1.3 min–1. The cell releases 40 fmol K+ during each burst of intermittent KCa channel activity, which corresponds to about 15% of the total cellular K+ content. Since transmembrane K+ loss must be accompanied by anion loss and therefore leads to a decrease of cell volume, these findings support the hypothesis that intermittent volume changes are a prerequisite for the migration of MDCK-F cells. Received: 15 April 1996 / Received after revision: 18 June 1996 / Accepted: 23 July 1996  相似文献   
54.
Method of creation computer models of upper floor of abdomen organs: liver, gallbladder, duodenum, pancreas, stomach, blood vessels with using computer system "DUCT" was described. Details of modelled structures of the cylindric and complicated forms were noted.  相似文献   
55.
Morphofunctional features of skin mast cells located in the areas subjected to chronic UV-radiation and in the associated basal cell carcinoma with photoinjure have been studied. Various immunohistochemical methods (chromogranin A, CDla, HLA-DR, CD35, Ki67, P53, Bcl-2, Mcl-1, involucrine) were used. It is found that chronic UV-damage leads to mast cell hyperplasia as well as activation of their synthetic, absorption and secretory functions. It is suggested that mast cell hyperplasia and increase of mast cells neuroendocrine activity provide a risk of basal cell carcinoma development.  相似文献   
56.
Gene P504S is considered as the most specific for prostatic carcinoma and its protein (alpha-methylacyl coenzyme A racemaze (AMACR/P504S) is higly sensitive and specific marker not only for adenocarcinoma cells but also for preceding changes - prostatic intraepithelial neoplasm (PIN). AMACR/P504S seems to be the first marker of malignant transformation and tumor progression. Use of immunohistochemical method for revealing this marker together with methods of basal prostatic cells observation (cytokeratin of a high molecular weight, cytokeratin 5/6, p63) improves morphological diagnosis of prostatic carcinoma, particularly on the material of needle biopsies. This combination allows one to identify neoplastic nature of some difficult lesions.  相似文献   
57.
Histological, histochemical and immunohistochemical studies of 50 solitary juvenile polyps (JP) and 50 JP from children with juvenile polyposis syndrome (JPS) were performed. Observations of the focal complex glandular structures with high mitotic rate were more frequent in JP from patients with JPS (n = 29, 58%) than in solitary JP (n = 17, 34%) (p < 0.03). The immunohistochemical study demonstrated p53 overexpression in individual cells and more than 50% of Ki-67-positive cells in 5 (10%) solitary JP and in 17(34%) JP from patients with JPS (p < 0.007). The finding of microglandular pattern is more typical for JP from patients with JPS. Pathological data, expression of p53 and Ki-67 by immunohistochemistry could help to pick out the group of JP with dysplastic changes.  相似文献   
58.
59.
Phylogenetic analysis of nucleotide sequences of gag and env genes of type 1 human immunodeficiency virus (HIV-1) variants isolated from individuals infected through sexual intercourse or nosocomially (by injections with nonsterile syringes) showed that 5 of 27 (18.5%) isolated strains were recombinants. Two viruses found in the Russian Far East had gagAenvE genotype, three other recombinants had envG genotype; gag gene of one isolate belonged to subtype A and gag genes of two others belonged to subtype D. Detection of new recombinant variants in addition to the A/B recombinant described previously shows that these viruses can contribute to the HIV-1 genetic variability in Russia.  相似文献   
60.
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