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991.
Nasef A Mathieu N Chapel A Frick J François S Mazurier C Boutarfa A Bouchet S Gorin NC Thierry D Fouillard L 《Transplantation》2007,84(2):231-237
INTRODUCTION: Mesenchymal stem cells (MSCs) possess unique immunomodulatory properties. They are able to suppress allogenic T-cell response and modify maturation of antigen-presenting cells. Their role in the treatment of severe graft versus host disease has been reported. The underlying molecular mechanisms of immunosuppression are currently being investigated. Histocompatibility locus antigen (HLA)-G is a nonclassical major histocompatibility complex class I antigen with strong immune-inhibitory properties. METHODS: We studied the role of HLA-G on MSC-induced immunosuppression. The expression of HLA-G on human MSCs cultured alone and in mixed lymphocytes reaction (MSC/MLR) was analyzed. RESULTS: We found that HLA-G can be detected on MSCs by real-time reverse-phase polymerase chain reaction, immunofluorescence, flow cytometry (52.4+/-3.6%), and enzyme-linked immunosorbent assay in the supernatant (38.7+/-5.2 ng/mL). HLA-G protein expression is constitutive and the level is not modified upon stimulation by allogenic lymphocytes in MSC/MLR. The functional role of HLA-G protein expressed by MSCs was analyzed using the 87G anti-HLA-G blocking antibody in a MSC/MLR. We found that blocking HLA-G molecule significantly raised lymphocyte proliferation in MSC/MLR (35.5%, P=0.01). CONCLUSION: Our findings provide evidences supporting involvement of HLA-G in the immunosuppressive properties of MSCs. These results emphasize the potential application of MSCs as a relevant therapeutic candidate in transplantation. 相似文献
992.
The regulatory/cytotoxic graft-infiltrating T cells differentiate renal allograft borderline change from acute rejection 总被引:3,自引:0,他引:3
Grimbert P Mansour H Desvaux D Roudot-Thoraval F Audard V Dahan K Berrehar F Dehoulle-Poillet C Farcet JP Lang P Le Gouvello S 《Transplantation》2007,83(3):341-346
The interpretation of cellular infiltrate from renal transplant recipients with borderline (BL) changes is still a challenging problem. To analyze the immune phenotype of such infiltrate, we quantified the mRNA expression of Foxp3 and interleukinL-10 and granzyme B (GB) in 15 kidney biopsies with BL changes. Controls were patients presenting type IA acute rejection and nonrejecting patients. Only levels of GB mRNA correlated significantly with response to antirejection therapy. Levels of Foxp3 mRNA in BL changes were intermediate between type IA acute rejection and nonrejecting controls. To determine the balance of alloagressive to graft-protecting T cells, we quantified the Foxp3/GB ratio. BL changes T cells infiltrate expressed a significantly higher Foxp3/GB ratio than that in IA acute rejection. These results suggest that T cell infiltrate from BL change exhibit a tolerogenic rather than a cytotoxic phenotype. 相似文献
993.
Sutcliffe S Rohrmann S Giovannucci E Nelson KE De Marzo AM Isaacs WB Nelson WG Platz EA 《The Journal of urology》2007,178(5):2181-2185
PURPOSE: Previous epidemiological studies described suggestive positive associations between sexually transmitted infections, particularly gonorrhea and human immunodeficiency virus infection, and lower urinary tract symptoms. To our knowledge no groups have investigated other infections, such as human papillomavirus type 16, herpes simplex virus type 2, cytomegalovirus, human herpesvirus type 8, herpes simplex type 1, and hepatitis B and C virus infection, in relation to lower urinary tract symptoms. Therefore, we examined each of these associations in the Third National Health and Nutrition Examination Survey. MATERIALS AND METHODS: The Third National Health and Nutrition Examination Survey is a representative, cross-sectional survey of the population in the United States that was done between 1988 and 1994. Each participant provided a blood sample and completed a computer assisted interview including questions on lower urinary tract symptoms (nocturia, incomplete emptying, hesitancy and weak stream). Blood samples were tested for IgG antibodies against each virus. RESULTS: In younger men (ages 30 to 49 years) positive associations were observed between cytomegalovirus, human herpesvirus type 8, herpes simplex virus type 1, and hepatitis B and C virus antibody seropositivity, and lower urinary tract symptoms. In 50 to 59-year-old men positive associations were observed between human papillomavirus type 16, herpes simplex virus type 2, cytomegalovirus, human herpesvirus type 8 and hepatitis C virus antibody seropositivity and lower urinary tract symptoms. In men 60 years or older only a slight, nonsignificant positive association was observed between cytomegalovirus antibody seropositivity and lower urinary tract symptoms. CONCLUSIONS: In this cross-sectional survey of American men suggestive positive associations were observed between several viral infections and lower urinary tract symptoms, primarily in 30 to 59-year-old men. These findings provide interesting hypotheses and preliminary evidence for future etiological studies of infections and lower urinary tract symptoms. 相似文献
994.
We tested and characterized the therapeutic value of round window membrane-delivered (RWM) d-JNKI-1 peptide (Bonny et al., 2001) against sound trauma-induced hearing loss. Morphological characteristics of sound-damaged hair cell nuclei labeled by Hoechst staining show that apoptosis is the predominant mode of cell death after sound trauma. Analysis of the events occurring after sound trauma demonstrates that c-Jun N-terminal kinase (JNK)/stress-activated protein kinase activates a mitochondrial cell death pathway (i.e., activation of Bax, release of cytochrome c, activation of procaspases, and cleavage of fodrin). Fluorescein isothiocyanate (FITC)-conjugated d-JNKI-1 peptide applied onto an intact cochlear RWM diffuses through this membrane and penetrates cochlear tissues with the exception of the stria vascularis. A time sequence of fluorescence measurements demonstrates that FITC-labeled d-JNKI-1 remains in cochlear tissues for as long as 3 weeks. In addition to blocking JNK-mediated activation of a mitochondrial cell death pathway, RWM-delivered d-JNKI-1 prevents hair cell death and development of a permanent shift in hearing threshold that is caused by sound trauma in a dose-dependent manner (EC50 = 2.05 microM). The therapeutic window for protection of the cochlea from sound trauma with RWM delivery of d-JNKI-1 extended out to 12 h after sound exposure. These results show that the mitogen-activated protein kinase/JNK signaling pathway plays a crucial role in sound trauma-initiated hair cell death. Blocking this signaling pathway with RWM delivery of d-JNKI-1 may have significant therapeutic value as a therapeutic intervention to protect the human cochlea from the effects of sound trauma. 相似文献
995.
Molenaar P Savarimuthu SM Sarsero D Chen L Semmler AB Carle A Yang I Bartel S Vetter D Beyerdörfer I Krause EG Kaumann AJ 《Naunyn-Schmiedeberg's archives of pharmacology》2007,375(1):11-28
Activation of either coexisting β1- or β2-adrenoceptors with noradrenaline or adrenaline, respectively, causes maximum increases of contractility of human atrial myocardium.
Previous biochemical work with the β2-selective agonist zinterol is consistent with activation of the cascade β2-adrenoceptors→Gsα-protein→adenylyl cyclase→cAMP→protein kinase (PKA)→phosphorylation of phospholamban, troponin I, and C-protein→hastened
relaxation of human atria from nonfailing hearts. However, in feline and rodent myocardium, catecholamines and zinterol usually
do not hasten relaxation through activation of β2-adrenoceptors, presumably because of coupling of the receptors to Gi protein. It is unknown whether the endogenously occurring
β2-adrenoceptor agonist adrenaline acts through the above cascade in human atrium and whether its mode of action could be changed
in heart failure. We assessed the effects of (-)-adrenaline, mediated through β2-adrenoceptors (in the presence of CGP 20712A 300 nM to block β1-adrenoceptors), on contractility and relaxation of right atrial trabecula obtained from nonfailing and failing human hearts.
Cyclic AMP levels were measured as well as phosphorylation of phospholamban, troponin I, and protein C with Western blots
and the back-phosphorylation procedure. For comparison, β1-adrenoceptor-mediated effects of (-)-noradrenaline were investigated in the presence of ICI 118,551 (50 nM to block β2-adrenoceptors). The positive inotropic effects of both (-)-noradrenaline and (-)-adrenaline were accompanied by reductions
in time to peak force and time to reach 50% relaxation. (-)-Adrenaline caused similar positive inotropic and lusitropic effects
in atrial trabeculae from failing hearts. However, the inotropic potency, but not the lusitropic potency, of (-)-noradrenaline
was reduced fourfold in atrial trabeculae from heart failure patients. Both (-)-adrenaline and (-)-noradrenaline enhanced
cyclic AMP levels and produced phosphorylation of phospholamban, troponin I, and C-protein to a similar extent in atrial trabeculae
from nonfailing hearts. The hastening of relaxation caused by (-)-adrenaline together with the PKA-catalyzed phosphorylation
of the three proteins involved in relaxation, indicate coupling of β2-adrenoceptors to Gs protein. The phosphorylation of phospholamban at serine16 and threonine17 evoked by (-)-adrenaline through
β2-adrenoceptors and by (-)-noradrenaline through β1-adrenoceptors was not different in atria from nonfailing and failing hearts. Activation of β2-adrenoceptors caused an increase in phosphorylase a activity in atrium from failing hearts further emphasizing the presence of the β2-adrenoceptor–Gsα-protein pathway in human heart. The positive inotropic and lusitropic potencies of (-)-adrenaline were conserved
across Arg16Gly- and Gln27Glu-β2-adrenoceptor polymorphisms in the right atrium from patients undergoing coronary artery bypass surgery, chronically treated
with β1-selective blockers. The persistent relaxant and biochemical effects of (-)-adrenaline through β2-adrenoceptors and of (-)-noradrenaline through β1-adrenoceptors in heart failure are inconsistent with an important role of coupling of β2-adrenoceptors with Giα-protein in human atrial myocardium. 相似文献
996.
Glasl S Tsendayush D Batchimeg U Holec N Wurm E Kletter C Gunbilig D Daariimaa K Narantuya S Thalhammer T 《Planta medica》2007,73(1):59-66
Saussurea amara is used in traditional Mongolian medicine for the treatment of hepato-biliary disorders. To determine the plant's effect on the bile-salt independent bile flow (hydrocholeresis) as a measure of liver exocrine functions, different extracts were investigated in the isolated rat liver perfusion system. The methanolic extract (3) exerted a dose-dependent increase in bile flow (16%, 37%, 53%, 61%) in concentrations of 50 mg/L, 100 mg/L, 250 mg/L and 500 mg/L. The aqueous crude extract (1) and the ethyl acetate extract (2) also showed a dose-dependent increase, whereas at the highest concentrations (1000 mg/L and 100 mg/L, respectively) a continuous decrease in bile flow could be observed. Cynaropicrin also provoked a dose-dependent increase in bile flow, but caused liver damage at the highest dose tested (20 mg/L). Apigenin 7- O-glucoside, present in extracts 2 and 3, induced a dose-dependent increase of 20%, 30% and 40% (5 mg/L, 10 mg/L, 20 mg/L) and showed a significantly higher effect than the reference substance cynarin. The total flavonoid content was determined by spectrophotometry. To quantify the absolute amount of cynaropicrin in the crude drug and in the tested extracts, an HLPC system was established with santonin as internal standard. 相似文献
997.
Thedinga E Kob A Holst H Keuer A Drechsler S Niendorf R Baumann W Freund I Lehmann M Ehret R 《Toxicology and applied pharmacology》2007,220(1):33-44
To characterize modes of action of substances and their cytotoxic effects Bionas GmbH has developed a new screening system to allow the continuous recording of how an active substance can act (Bionas 2500 analyzing system). In the pharmaceutical industry it is important to acquire as much information as possible about the metabolic effects of an active substance. Most classical pre-clinical studies are very expensive and time-consuming. Often they are so-called end-point tests which require many individual tests before approximate statements can be made about how an effect takes its course. With the Bionas 2500 analyzing system metabolically relevant data including oxygen consumption, acidification rate and the adhesion (cell impedance) of cells can be measured in parallel, online and label-free. Using e.g. ion-sensitive field effect-transistors (ISFET) and electrode structures it is possible to observe metabolic parameters non-invasively and continuously over longer periods of time. The system has already been established for several cell models, cell lines as well as primary cells. It also offers the advantage that regenerative effects can be observed during the same test run. 相似文献
998.
Krause S Schlotter-Weigel B Walter MC Najmabadi H Wiendl H Müller-Höcker J Müller-Felber W Pongratz D Lochmüller H 《Neuromuscular disorders : NMD》2003,13(10):830-834
An adult-onset hereditary inclusion body myopathy with sparing of the quadriceps muscle was originally described in Iranian Jews and assigned to a locus on chromosome 9p12–p13. Recently, mutations of the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) gene were reported to cause hereditary inclusion body myopathy and one type of distal myopathy in a world-wide distribution. Importantly, the lack of muscle inflammation was used to distinguish hereditary inclusion body myopathy from the sporadic form of inclusion body myopathy. We report a case of a quadriceps-sparing myopathy in a non-Jewish, Iranian patient with a high degree of muscle inflammation. A novel homozygous G-to-A mutation (128933G→A) in exon 7 changing a valine to isoleucine (V367I) in the epimerase domain of the GNE gene was found. We conclude that muscle inflammation is not sufficient to exclude the diagnosis of hereditary inclusion body myopathy. 相似文献
999.
Socioeconomic status is a major determinant of coronary heart disease (CHD). Proinflammatory cytokines are implicated in the etiology of CHD, and are also sensitive to emotional stress. We hypothesised that concentration of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 receptor antagonist (IL-1Ra) would be inversely related to socioeconomic status, and that cytokine responses to stress would be associated with SES. One hundred and twenty-five middle-aged men and 105 women from the Whitehall II epidemiological cohort were tested, and socioeconomic status was indexed by grade of employment, with participants divided into high, intermediate, and low status groups. Plasma concentrations at rest of TNF-alpha, IL-1Ra, and IL-6 (women only) were associated with socioeconomic status, with lower levels in the high status group, but the effect was non-linear. There was no relationship between socioeconomic status and cytokine responses to stress, but sex differences were observed, with men showing greater TNF-alpha, and women greater IL-6 and IL-1Ra increases. The role of inflammatory cytokines in mediating psychosocial influences on CHD is discussed. 相似文献
1000.
Ellen Rose Sabine Wever Detlef Zillikens Ruthild Linse Uwe‐Frithjof Haustein Eva‐Bettina Brcker 《Journal der Deutschen Dermatologischen Gesellschaft》2005,3(3):200-206
Background: Pemphigus is a potentially life‐threatening autoimmune blistering skin disease usually treated with high‐dose corticosteroids in combination with immunosuppressive drugs. In a multicenter, prospectively randomized study we compared efficacy and side effects of a dexamethasone‐cyclophosphamide (D/C) pulse therapy with a methylprednisolone‐azathioprine (M/A) therapy in 22 patients with newly diagnosed pemphigus vulgaris and pemphigus foliaceus. Patients and methods: The 11 patients of the M/A group were treated with daily doses of methylprednisolone (initially 2 mg/kg body weight) and azathioprine (2 – 2,5 mg/kg body weight) which were subsequently tapered. D/C pulse therapy in 11 patients consisted of intravenous administration of 100 mg dexamethasone/d on 3 consecutive days along with cyclophosphamide (500 mg) on day one. Pulses were initially repeated every 2 – 4 weeks and then at increasing intervals. In between the pulses, oral cyclophosphamide (50 mg) was given daily for 6 months. Results: Within 24 months after treatment initiation, 5/11 patients of the D/C group had a remission (complete remissions after discontinuation of therapy in 3 patients) and 6/11 patients had a progression. In the M/A group, there were remissions in 9/11 patients (complete remissions after discontinuation of therapy in 3 patients) and progression in 1/11 patients. There were more relapses in M/A therapy after remission than in D/C therapy. Side effects were more common in the M/A group. These differences were not significant (p > 0,05). Conclusion: Because of the high number of progressions in patients treated with D/C therapy, we can not confirm the encouraging results of earlier reports about pulse D/C therapy. Nevertheless D/C therapy seemed to be better tolerated and, in case of primary efficacy, was associated with fewer recurrences than M/A therapy. 相似文献