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61.
New trends in the design of drugs against Alzheimer's disease 总被引:1,自引:0,他引:1
Francotte P Graindorge E Boverie S de Tullio P Pirotte B 《Current medicinal chemistry》2004,11(13):1757-1778
First described by Alois Alzheimer in 1907, Alzheimer's disease (AD) is the most common dementia type, affecting approximately 20 million people worldwide. As the population is getting older, AD is a growing health problem. AD is currently treated by symptomatic drugs, the acetylcholinesterase inhibitors, based on the cholinergic hypothesis (1976). During the past decade, advances in neurobiology have conducted to the identification of new targets. Although some of these innovative approaches tend to delay onset of AD, others are still symptomatic. In this review, we present an overview of the several strategies and new classes of compounds against AD. 相似文献
62.
Cuffini AM Tullio V Mandras N Roana J Scalas D Banche G Carlone NA 《International journal of tissue reactions》2002,24(1):37-44
There is an urgent need for antibiotics that can be used in the therapy of infections caused by penicillin-resistant Streptococcus pneumoniae, the incidence of which is often associated with considerable morbidity and mortality. Antibiotics that can interact positively with the immune response and that also possess microbicidal properties might significantly contribute to improving the outcome of S. pneumoniae infections. Therefore, in the present study we investigated the effect of clarithromycin, an extended spectrum macrolide currently used in the treatment of respiratory tract infections, on the in vitro interaction between human polymorphonuclear granulocytes (PMN) and three strains of S. pneumoniae with different susceptibility or resistance patterns to both penicillin and clarithromycin. At a concentration of one-half the minimal inhibitory concentration (MIC), clarithromycin significantly enhanced human PMN functions, particularly intracellular bactericidal activity, against all the S. pneumoniae strains, including resistant ones. This finding may help to explain clarithromycin activity in vivo despite apparent resistance in vitro. Preexposure of PMNs to one-half the MIC of clarithromycin had no effect on either phagocytosis or intracellular killing, ruling out a direct antibiotic action on PMNs. Preexposure of streptococci to clarithromycin increased the susceptibility of S. pneumoniae to the bactericidal mechanisms of human PMNs compared with untreated bacteria, indicating that this macrolide may partly reduce bacterial virulence via changes in S. pneumoniae. 相似文献
63.
64.
Hepatitis C virus-related cryoglobulinemic glomerulonephritis: long-term remission after antiviral therapy 总被引:8,自引:0,他引:8
Rossi P Bertani T Baio P Caldara R Luliri P Tengattini F Bellavita P Mazzucco G Misiani R 《Kidney international》2003,63(6):2236-2241
BACKGROUND: Renal involvement in patients with hepatitis C virus (HCV) infection commonly manifests as cryoglobulinemic glomerulonephritis (CGN). The combination of interferon-alpha (IFN-alpha) and ribavirin, which is currently considered the standard antiviral therapy in chronic hepatitis C, could be difficult to carry out in cryoglobulinemic patients who are frequently anemic, even in the absence of renal failure. Clinical and histologic long-term results of this therapeutic regimen have not been so far reported in patients with CGN. METHODS: Three patients with HCV-related CGN and slightly impaired kidney function were treated with IFN-alpha and ribavirin for 12 months, and subsequently were followed up for 24 to 36 months. Two of these patients who were anemic were pretreated with erythropoietin (EPO). In each patient renal biopsy was performed before starting therapy and repeated 14 to 26 months after the end of treatment. RESULTS: In all three patients, antiviral therapy induced sustained virologic response, which was followed by clear improvement in clinical, biochemical, immunologic, and histologic features. Clinical and biochemical improvement steadily progressed in all three patients, achieving normal or nearly normal results at the end of follow-up. In contrast, some immunologic features, such as serum levels of C4 and rheumatoid factor activity, did not normalize in two and three patients, respectively. Posttreatment renal biopsies showed mildly active histologic lesions. CONCLUSION: Antiviral therapy with IFN-alpha and ribavirin may be considerably beneficial in patients with HCV-related CGN who obtain sustained virologic response. 相似文献
65.
Stromal cell-derived factor 1alpha stimulates human glioblastoma cell growth through the activation of both extracellular signal-regulated kinases 1/2 and Akt 总被引:18,自引:0,他引:18
Barbero S Bonavia R Bajetto A Porcile C Pirani P Ravetti JL Zona GL Spaziante R Florio T Schettini G 《Cancer research》2003,63(8):1969-1974
In this paper, we describe the role of chemokine receptor CXCR4 activation by its natural ligand, the chemokine stromal cell-derived factor (SDF-1) (CXCL12), in glioblastoma cell growth in vitro. We show that both CXC chemokine receptor 4 (CXCR4) and SDF-1 mRNA are expressed in several human glioblastoma multiforme tumor tissues and in two human glioblastoma cell lines, U87-MG and DBTRG-05MG. These cells are able to secrete SDF-1 under basal conditions, and the rate of secretion is highly increased after lipopolysaccharide or 1% fetal bovine serum treatment. Exogenous SDF-1alpha induces proliferation in a dose-dependent manner in both cell lines. Moreover, we observed that SDF-1alpha-dependent proliferation is correlated with phosphorylation and activation of both extracellular signal-regulated kinases 1/2 and Akt and that these kinases are independently involved in glioblastoma cell proliferation. The role of CXCR4 stimulation in glioblastoma cell growth is further demonstrated by the ability of human monoclonal CXCR4 antibody (clone 12G5) to inhibit the SDF-1alpha-induced proliferation as well as the proliferation induced by SDF-1-releasing treatments (lipopolysaccharide and 1% fetal bovine serum). These data support a role for SDF-1alpha in the regulation of glioblastoma growth in vitro, likely through an autocrine/paracrine mechanism. 相似文献
66.
Determination of the in vivo effects of prednisone on Bcl-2 family protein expression in childhood acute lymphoblastic leukemia 总被引:1,自引:0,他引:1
Casale F Addeo R D'Angelo V Indolfi P Poggi V Morgera C Crisci S Di Tullio MT 《International journal of oncology》2003,22(1):123-128
Glucocorticoid resistance is often associated with treatment failure in children with acute lymphoblastic leukaemia (ALL) but the underlying molecular mechanisms are still unclear. In 30 consecutive children with ALL treated with prednisone we determined changes in the expression of Bcl-2, Bax and Bcl-xl proteins in leukemic lymphoblasts and related these to clinical features and rate of prednisone-induced apoptosis. The apoptotic index increased after prednisone therapy in 24 of the 30 patients. At diagnosis, we detected expression of Bcl-2 and Bcl-xl protein in 28 samples, while Bax expression protein was detected in 21 of the 30 patients. Prednisone treatment induced a decrease in Bcl-2 and Bcl-xl levels in 17 and 16 of the 28 patients, respectively, while Bax protein increased in 14 of the 21 patients. Twenty of the 30 patients studied were considered to be good prednisone responders, whereas 10 were poor responders. We observed a statistically significant decrease only for Bcl-xl protein expression in T phenotype ALL, in the poor responder group and in patients with >20000/mm(3) white cell count (WBC) at diagnosis. These data suggest a role of Bcl-xl in the mechanisms of protection of leukemic cells from apoptosis induced by glucocorticoids (GCs). 相似文献
67.
Bonavia R Bajetto A Barbero S Pirani P Florio T Schettini G 《Toxicology letters》2003,139(2-3):181-189
The study of chemokine role in the CNS indubitably represents an important step to understanding many aspects of brain pathology, physiology and development. Here we discuss our recent research on the expression of chemokines and chemokine receptors in brain tissues and in cultured CNS cells, with particular regard to the CXCL12/SDF-1-CXCR4 system. We showed their expression in both glial and neuronal cells in basal conditions and their modulation upon stimulation. We demonstrated that CXCL12/SDF-1 in vitro act as a growth factor for astrocytes by stimulating their proliferation, a phenomenon that could represent the basis of pathological conditions such as gliosis and malignant transformation. We investigated the signal transduction pathways, identifying in the sequential activation of G-protein-PI-3Kinase-ERK1/2 the main signaling cascade linked to the CXCL12/SDF-1-induced proliferation in astrocytes. 相似文献
68.
Zivadinov R Uxa L Zacchi T Nasuelli D Ukmar M Furlan C Pozzi-Mucelli R Tommasi MA Locatelli L Ulivi S Bratina A Bosco A Grop A Cazzato G Zorzon M 《Journal of neurology》2003,250(9):1099-1106
The objective of the study was to examine the relationship
between HLA genotypes and disease severity as measured by brain
MRI quantitative markers of demyelinating and destructive
pathology in patients with multiple sclerosis (MS). We studied
100 patients with MS and 122 age, sex-, ethnic- and
residence-matched controls. The DNA extraction and the genomic
typing (A, B, DRB1 and DQB1 loci) were obtained with
sequence-specific oligonucleotide method, using a commercially
available reversible line blot assay (INNO-LIPA). All patients
underwent a 1.5 tesla MRI examination of the brain. Disease
severity was assessed by clinical (Expanded Disability Status
Scale (EDSS)) and MRI (T2- and T1-lesion load (LL) and brain
parenchymal fraction (BPF)) outcome measures. HLA-DQB1* 02 (OR
19.9, 95% C. I. 16.2–24.3, uncorrected (uncorr)- p<0.00001,
corr-p<0.0006), -DQB1*03 (OR 16.8, 95% C. I. 13.6–20.5,
uncorr-p<0.00001, corrp< 0.0006), -DRB1*15 (OR 4.6, 95% C.
I. 3.7–5.6, uncorrp= 0.0001, corr-p=0.006), and -DRB1*03 (OR
3.9, 95% C. I. 3.2–4.8, uncorr-p=0.0001, corrp= 0.006) alleles
were associated with MS. T2-, T1-LL, BPF and EDSS were not
significantly different according to the carrier status of these
HLA alleles. No differences were found in the ratios of disease
severity/disease duration according to the HLA car rier status.
Multiple regression analysis showed that a higher T2-LL was
associated with the presence of DRB1*04 (uncorr- R2=0.15,
p=0.006 and corr- R2=0.11, p=0.025) and B7 alleles
(uncorr-R2=0.08, p=0.02 and corr-R2=0.07, p=0.018), T1-LL was
associated with B7 (uncorr- R2=0.30, p<0.0001 and corr-
R2=0.27, p=0.0001) and DRB1*12 (uncorr-R2=0.25, p<0.0001 and
corr-R2=0.21, p=0.0002) alleles, whereas the BPF was predicted
only by the presence of DRB1*12 allele (uncorr-R2=0.24, p=0.002
and corr-R2=0.20, p=0.004). The study findings suggest that some
HLA alleles may predict the destructive pathological processes
visible on MRI. Since the size of the sample studied is
relatively small, further studies are needed to draw any firm
conclusion about genotype/phenotype correlation in patients with
MS. 相似文献
69.
Tullio Meloni Sergio Erre Domenico Gallisai Stefano Cutillo 《European journal of pediatrics》1980,134(2):119-120
Hb A2 was determined in 50 subjects with erythrocyte G-6-PD deficiency who presented with hyperbilirubinemia in the neonatal period and in 100 non-hyperbilirubinemic G-6-PD deficient newborn infants, at the age of 12 months or more. Six subjects in the first group and 13 in the second were found to be carriers of the -thalassemia trait. Statistical analysis of the data did not show any significant difference between the two groups. It seems that the -thalassemia trait does not provide any protection against neonatal hyperbilirubinemia associated with G-6-PD deficiency. 相似文献
70.