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排序方式: 共有908条查询结果,搜索用时 15 毫秒
61.
LAMA2 gene analysis in congenital muscular dystrophy: new mutations, prenatal diagnosis, and founder effect 总被引:2,自引:0,他引:2
Di Blasi C Piga D Brioschi P Moroni I Pini A Ruggieri A Zanotti S Uziel G Jarre L Della Giustina E Scuderi C Jonsrud C Mantegazza R Morandi L Mora M 《Archives of neurology》2005,62(10):1582-1586
OBJECTIVE: To determine if laminin-alpha2 deficiency is due to mutations in the LAMA2 gene or secondary to mutations in other congenital muscular dystrophy genes. METHODS: We performed molecular analysis of LAMA2, by single-strand conformation polymorphism and sequencing, in 15 patients with undetectable or greatly reduced laminin-alpha2 expression. We also performed 4 prenatal diagnoses and investigated a founder effect. RESULTS: We found 1 known and 9 previously undescribed LAMA2 mutations spanning all protein domains. These were nonsense or frameshifts causing laminin-alpha2 absence or, in 1 case, a homozygous missense mutation producing partial protein expression and milder phenotype. LAMA2 mutations were undetected in 5 patients, in 2 of whom FKRP mutations explained the phenotype. In 3 prenatal cases, the fetus was heterozygous for the mutation of interest and pregnancy continued; in 1 case, the fetus was affected and aborted. In 2 patients, the Cys967Stop mutation and identical haplotypes flanking the LAMA2 gene indicated a founder effect. CONCLUSIONS: The clinical phenotype was severe in most patients with LAMA2 mutations and associated with undetectable protein expression. One case with no protein and another with partial expression had milder phenotypes. Typical white matter alterations on magnetic resonance imaging were found in all patients with LAMA2 mutations, supporting the utility of magnetic resonance imaging in differential diagnosis. The founder mutation (Cys967Stop) probably originated in Albania. Genetic characterization of affected families is mainly of use for prenatal diagnosis. 相似文献
62.
Mechanisms in prostatitis/chronic pelvic pain syndrome 总被引:31,自引:0,他引:31
PURPOSE: We reviewed the current literature on mechanisms involved in the pathogenesis of prostatitis/chronic pelvic pain syndrome (CPPS). MATERIALS AND METHODS: A literature review for the years 1966 to 2003 was performed using the MEDLINE database of the United States National Library of Medicine. RESULTS: National Institutes of Health categories I and II prostatitis result from identifiable prostatic infections, whereas patients with category IV are asymptomatic. The majority of symptomatic cases are category III or chronic prostatitis (CP)/CPPS. The etiology of CP/CPPS is unknown. The traditional marker of inflammation, namely white blood cells in prostatic fluids, does not correlate with the predominant symptom of pelvic pain. An imbalance toward increased proinflammatory and decreased anti-inflammatory cytokines has been implicated and a few studies have shown some correlation of this with pelvic pain. The imbalance in some men may result from polymorphisms at the cytokine loci. An autoimmune process may be involved and experimental evidence indicates that this can be under hormonal influence. Recent findings include possible defects in the androgen receptor. The prostate may not even be the source of the symptoms. Pelvic pain also correlates with the neurotrophin nerve growth factor implicated in neurogenic inflammation and central sensitization. Finally, psychological stress may produce measurable biochemical changes and influence the other processes. The role of normal prostatic bacterial flora in inciting the inflammatory response has also been reconsidered. CONCLUSIONS: The symptoms of CP/CPPS appear to result from an interplay between psychological factors and dysfunction in the immune, neurological and endocrine systems. 相似文献
63.
Ruggieri R 《Physics in medicine and biology》2004,49(20):4811-4823
Based on experimental estimates for acute and chronic tumour hypoxia, a speculative analysis of the therapeutic ratio dependence on the number of once-daily five-days-per-week fractions (n) for non-small cell lung cancer (NSCLC) radiotherapy is proposed. For this purpose an adapted formulation of the linear-quadratic model has been derived, including the effects of tumour repopulation, inter-tumour alpha-heterogeneity and oxygen enhancement ratio dependence on the dose per fraction. The relation between the curative dose D50, assuring 50% tumour control probability, and n has been computed: for (n, D50) fractionation schemes, the therapeutic ratios have been compared in terms of effective normalized total doses to the lungs (NTD(eff)L), estimated by a few supposed fractions of the normalized total dose to the tumour. Results suggest that D50 is dominated by chronic hypoxia for shortly hypofractionated treatments and by acute hypoxia for multifractionated treatments. Furthermore, the optimum number of fractions depends on the rapidity of the reoxygenation from chronically hypoxic cells, almost independently of the extent of both chronic and acute hypoxia. For NSCLC, both the reduction of n until about 20 fractions in hypofractionated dose-escalation trials, and the extension of extra-cranial stereotactic radiotherapy schedules to include at least 5-10 fractions, seem to be supported by this model. 相似文献
64.
Epilepsy is not a prominent feature of primary autism 总被引:6,自引:0,他引:6
Pavone P Incorpora G Fiumara A Parano E Trifiletti RR Ruggieri M 《Neuropediatrics》2004,35(4):207-210
The authors report on a series of 72 patients (57 male, 15 female; aged from 4 to 21 years) affected by autism with the aim of evaluate their experience regarding the prevalence of seizure and/or epilepsy. Patients were divided into two groups: the first includes individuals (n = 54) affected by so-called idiopathic or primary autism which was further subdivided according to the grade of mental retardation (MR) and the second (n = 18) in which a known pathological event was associated to the autism (secondary autism). According to these results in the first group 12 % of autistic patients with moderate MR (i.e., IQ > 55) suffered from seizures but in three patients (9 %) they were occasional and only in one recurrent (i.e., epileptic) (3 %). Autistic patients with severe MR (i.e., IQ < 55) suffered from seizures in 20 % of the cases: in three the episodes were recurrent (15 %) and in one occasional (5 %). In the second group in which autism was associated to other morbidities 61 % (n = 11/18) had seizures, being recurrent in 10 (55 %). According to this series, in autism the risk of epilepsy is higher compared to the general population but it does not seem to be correlated to the autism itself, but rather to the associated co-morbidities and underlying brain dysfunction (overall prevalence of epilepsy in primary autism [4/54 or 7.4 %] vs. secondary autism [10/18 or 55 %]). 相似文献
65.
Magni G Amici A Emanuelli M Orsomando G Raffaelli N Ruggieri S 《Current medicinal chemistry》2004,11(7):873-885
The enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT), a member of the nucleotidyltransferase alpha/beta phosphodiesterase superfamily, catalyzes the reaction NMN + ATP = NAD + PPi, representing the final step in the biosynthesis of NAD, a molecule playing a fundamental role as a cofactor in cellular redox reactions. NAD also serves as the substrate for reactions involved in important regulatory roles, such as protein covalent modifications, like ADP-ribosylation reactions, as well as Sir2 histone deacetylase, a recently discovered class of enzymes involved in the regulation of gene silencing. This overview describes the most recent findings on NMNATs from bacteria, archaea, yeast, animal and human sources, with detailed consideration of their major kinetic, molecular and structural features. On this regard, the different characteristics exhibited by the enzyme from the various species are highlighted. The possibility that NMNAT may represent an interesting candidate as a target for the rational design of selective chemotherapeutic agents has been suggested. 相似文献
66.
The aim of the present work was to evaluate the effect of bendazac lysine on the human lens epithelial cell line HLE-B3 adhesion to polymethylmethacrylate (PMMA) intraocular lenses (IOLs). After adherence to IOLs, cells were incubated in the presence of the drug for 24 h. The number of cells contained in a 6-mm(2) area was then counted with an inverted phase microscope and adherent cells were distinguished from detached floating cells by focusing through the medium. Results obtained show that bendazac is able to induce a linear dose-dependent inhibition of HLE-B3 adhesiveness to PMMA IOLs. In particular, treatment with bendazac 33, 100 and 300 microM resulted in a 15, 32 and 54% inhibition, respectively. Statistical analysis shows that this effect is significant at 100 microM (p < 0.05) and 300 microM (p < 0.01). The analysis of the effects of bendazac on the viability and on the proliferative capacity of HLE-B3 cells did not show any drug-related toxicity up to the concentration of 400 microM. The present study demonstrates that bendazac lysine is able to inhibit adhesion of lens epithelial cells to PMMA IOLs and suggests the potential beneficial use of this drug in preventing secondary cataract development. 相似文献
67.
Fornai F Lenzi P Frenzilli G Gesi M Ferrucci M Lazzeri G Biagioni F Nigro M Falleni A Giusiani M Pellegrini A Blandini F Ruggieri S Paparelli A 《Psychopharmacology》2004,173(3-4):353-363
Rationale 3,4-Methylenedioxymethamphetamine (MDMA) is an amphetamine derivative, which is neurotoxic to both serotonin (5HT) and dopamine (DA) nerve terminals. Previous reports, carried out in rodents and non-human primates, demonstrated neurotoxicity to monoamine axon terminals, although no study has analyzed nigral and striatal cell bodies at the sub-cellular level.Objective In this study, we examined intrinsic nigral and striatal cells, and PC12 cell cultures to evaluate whether, in mice, MDMA might affect nigral and striatal cell bodies.Methods After administering MDMA, we analyzed effects induced in vivo and in vitro using high-performance liquid chromatography (HPLC) analysis, light- and electron microscopy with immunocytochemistry, and DNA comet assay.Results We found that MDMA (5 mg/kg ×4, 2 h apart), besides a decrease of nigrostriatal DA innervation and 5HT loss, produces neuronal inclusions within nigral and intrinsic striatal neurons consisting of multi-layer ubiquitin-positive whorls extending to the nucleus of the cell. These fine morphological changes are associated with clustering of heat shock protein (HSP)-70 in the nucleus, very close to chromatin filaments. In the same experimental conditions, we could detect oxidation of DNA bases followed by DNA damage. The nature of inclusions was further investigated using PC12 cell cultures.Conclusions The present findings lead to re-consideration of the neurotoxic consequences of MDMA administration. In fact, occurrence of ubiquitin-positive neuronal inclusions and DNA damage both in nigral and striatal cells sheds new light into the fine alterations induced by MDMA, also suggesting the involvement of nuclear and cytoplasmic components of the ubiquitin-proteasome pathway in MDMA toxicity. 相似文献
68.
In utero exposure to di-(2-ethylhexyl)phthalate and duration of human pregnancy 总被引:11,自引:0,他引:11 下载免费PDF全文
Latini G De Felice C Presta G Del Vecchio A Paris I Ruggieri F Mazzeo P 《Environmental health perspectives》2003,111(14):1783-1785
Di-(2-ethylhexyl)phthalate (DEHP), the most commonly used plasticizer in flexible polyvinylchloride formulations, is a ubiquitous environmental contaminant. To date, no information exists on the potential health hazards from exposure to DEHP and/or its main metabolite, mono-(2-ethylhexyl)phthalate (MEHP), in high-risk conditions, such as pregnancy and during the neonatal period. The aim of this study was to evaluate prenatal exposure to DEHP and/or MEHP and its possible biologic effects. We measured serum DEHP and MEHP concentrations in the cord blood of 84 consecutive newborns by high-performance liquid chromatography. Relationships between DEHP/MEHP and infant characteristics were tested using Fisher's exact test, unpaired t-tests, and univariate linear regression analyses, and significant differences on univariate analysis were evaluated using multiple logistic regression analysis. We found detectable cord blood DEHP and/or MEHP concentrations in 88.1% of the samples. Either DEHP or MEHP was present in 65 of 84 (77.4%) of the examined samples. Mean concentrations of DEHP and MEHP were 1.19 +/- 1.15 microg/mL [95% confidence interval (CI), 0.93-1.44, range = 0-4.71] and 0.52 +/- 0.61 microg/mL (95% CI, 0.39-0.66, range = 0-2.94), respectively. MEHP-positive newborns showed a significantly lower gestational age compared with MEHP-negative infants (p = 0.033). Logistic regression analysis results indicated a positive correlation between absence of MEHP in cord blood and gestational age at delivery (odds ratio = 1.50, 95% CI, 1.013-2.21; p = 0.043). These findings confirm that human exposure to DEHP can begin in utero and suggest that phthalate exposure is significantly associated with a shorter pregnancy duration. 相似文献
69.
F. Fornai G. Lazzeri P. Lenzi M. Gesi M. Ferrucci P. Soldani A. Pellegrini L. Capobianco A. De Blasi S. Ruggieri A. Paparelli 《Neurological sciences》2003,24(3):182-183
Abstract.
The present study explores whether effects induced by
amphetamine derivatives on striatal GABA cells might be
connected with effects on dopamine (DA) metabolism.
Methamphetamine (METH) and 3,4-methylenedioxymethamphetamine
(MDMA, ecstasy) were administered to C57Black mice following a
dosage regimen in which various doses of both drugs were
injected i.p. at 2-h intervals. Neuronal inclusions produced
under these experimental conditions were examined under electron
microscopy. Drugs reducing DA availability prevented inclusion
formation; conversely we observed that increasing DA synthesis
or impairing physiological DA degradation enhanced the number of
inclusions. The present study indicates that the presence of
extracellular striatal DA is essential for the production of
subcellular alterations induced by amphetamine derivatives. This
is in line with a recent hypothesis connecting striatal DA
release with degeneration of striatal GABA neurons. 相似文献
70.
Avolio C Ruggieri M Giuliani F Liuzzi GM Leante R Riccio P Livrea P Trojano M 《Journal of neuroimmunology》2003,136(1-2):46-53
In multiple sclerosis (MS), matrix metalloproteinase (MMP) activity in tissues is the result of a balance between MMPs and their tissue inhibitors (TIMPs). MMP-9 predominates in acute MS lesions and is inhibited by TIMP-1, while MMP-2 may participate in the remodeling of the extracellular matrix (ECM) such as in chronic disease and is inhibited by TIMP-2. These differences may be reflected in serum and cerebrospinal fluid (CSF). We have tried to characterize MMP-2 and MMP-9 activities, in relation to their respective TIMPs, 2 and 1, as a factor of different types of the disease, as this information was not previously clearly stated. We found the MMP-2/TIMP-2 ratio in serum to show higher values in secondary progressive (SP, p=0.02) and primary progressive (PP, p=0.01) MS than short disease duration (SDD) relapsing-remitting (RR) MS, but not different from the healthy control (HC) group. Whereas the MMP-9/TIMP-1 ratio in serum showed higher (p=0.04) values in SDD RR MS than PP but also in active patients, evaluated either clinically (p=0.006) or from the magnetic resonance imaging (MRI, p<0.05), compared to inactive disease. CSF MMP to TIMP ratios did not differ between MS subtypes, suggesting systemic rather CNS-restricted changes. These results show that an increase in MMP-2/TIMP-2 ratio marks chronic progression in MS, but it is as high as in HC, and also confirm that high MMP-9 activity characterizes short duration relapsing and active forms of the disease. 相似文献