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101.
Decreased cerebrospinal fluid levels of neutral and basic amino acids in patients with Parkinson''s disease 总被引:4,自引:0,他引:4
Jos Antonio Molina Flix Javier Jimnez-Jimnez Pilar Gmez Carmela Vargas Jos Antonio Navarro Miguel Ortí-Pareja Teresa Gasalla Julin Benito-Len Flix Bermejo Joaquín Arenas 《Journal of the neurological sciences》1997,150(2):256-127
We measured the CSF levels of 21, and the plasma levels of 26, amino acids in 31 patients with Parkinson's disease (PD) and in 45 matched controls. We used an ion-exchange chromatography method. When compared to controls, PD patients had lower CSF levels of taurine, alanine, valine, leucine, isoleucine, ethanolamine, citrulline, ornithine, lysine, histidine, arginine, and alpha-aminobutyric acid. PD patients not treated with levodopa or with dopamine agonists had higher CSF tyrosine and phenylalanine levels than those not treated with these drugs and also than controls. PD patients had higher plasma levels of phosphoserine, threonine, methionine, tyrosine, sarcosine and -aminoadipic acid, and lower plasma levels of valine, leucine, and tryptophan, than controls. The CSF/plasma ratio of many of these amino acids was significantly lower in PD patients than those of controls, suggesting that PD patients might have a dysfunction in the transport of neutral and basic amino acids across the blood–brain barrier. 相似文献
102.
The present investigation was designed to study the dendritic tree of the Purkinje cells surviving after prenatal (Pre B) or neonatal (Neo B) exposure to phenobarbital (PhB). Prenatal exposure in mice was accomplished transplacentally by feeding the pregnant mother 3 g PhB/kg milled food on getation days 9 to 18. Neonatal exposure was conducted directly by injecting the neonates daily (50 mg PhB/kg) on postnatal days 2 to 21. Brains were removed at 14, 21, and 50 days of age. They were cut in the sagittal plane and prepared according to the Golgi method for analysis of the Purkinje cells dendrites. A few brains of 50-day-old Neo B and controls were cut and stained with hemotoxylin and eosin for the assessment of number of Purkinje cells. Neonatal PhB exposure caused 9% reduction in the number of dendritic spines per millimeter at age 14 and 21 days. This deficit was only transient as it disappeared by day 50. However, when the injection dose was reduced to 40 mg PhB/kg the deficits persisted to day 50. Possibly, selection against the most affected individuals accounted for the lesser effect of the higher dose. Prenatal PhB exposure had no long-lasting effect on the dendritic spines. No deficit in the area of the dendritic tree or the number of branches of all orders could be detected in any of the PhB-treated groups studied. Early PhB administration which had severe effects on the neuronal number, had a relatively small effect on the dendrites of the surviving Purkinje cells. Unlike some milder insults, it did not decrease the ratio of granule cells: Purkinje cells, and it is possible that the dendritic effects were dependent on changes in this ratio. 相似文献
103.
A mutated p53 status did not prevent the induction of apoptosis by sulforaphane,a promising anti-cancer drug 总被引:2,自引:0,他引:2
Fimognari C Sangiorgi L Capponcelli S Nüsse M Fontanesi S Berti F Soddu S Cantelli-Forti G Hrelia P 《Investigational new drugs》2005,23(3):195-203
Summary We investigated apoptosis induction by sulforaphane on three cell lines characterized by a different p53 status. In particular, we used p53-knock-out fibroblasts from newborn mice transfected with the p53-Ser220 mutation, observed in Li-Fraumeni Syndrome patients, as a model of mutated p53 status. Moreover, immortalized fibroblasts from newborn mice expressing or lacking p53 (p53 +/+ andp53-/-, respectively) have been used to verify whether mutated p53 status could prevent sulforaphane-induced apoptotic events. Sulforaphane was able to induce apoptosis on all three cell lines. Indeed, the caspase-3 assays and poly(ADP-ribose)polymerase (PARP) cleavage data indicated that sulforaphane stimulated caspase-3-like activity and degradation of PARP. However, cells with a wild-type or mutated p53 appeared to be more sensitive to the effects of sulforaphane than cells lacking p53. Taken together, our results suggest that sulforaphane could act by a p53-independent pathway. For this reason, sulforaphane can be viewed as a novel agent useful not only in the treatment of Li-Fraumeni-associated tumors but also drug resistant tumors where p53 dysregulation is a feature. 相似文献
104.
BACKGROUND: Intraductal papillary mucinous tumors (IPMT) account for 5% of pancreatic neoplasms. Preoperative identification is important because of their frequent multifocal or diffuse involvement in pancreatic ducts, which makes extensive surgery necessary even in benign cases. To the authors' knowledge, the cytologic features of this entity in fine-needle aspiration biopsy (FNAB) specimens have seldom been described and are poorly standardized. METHODS: Eleven consecutive cases of surgically proven IPMT with previous endoscopic ultrasonography (EUS)-guided FNAB were collected for retrospective analysis. EUS-FNAB had been performed with on-site attendance of a cytopathologist in all cases. Macroscopic and microscopic appearance of mucin, cellular type and arrangement, presence of nuclear grooves, and degree of nuclear atypia were recorded. RESULTS: Final diagnosis was benign IPMT (B) in four cases, borderline IPMT (Bo) in two cases, malignant IPMT (M) in one case, and IPMT associated with invasive carcinoma (Ca) in four. Retrospective analysis found moderate to high levels of extracellular mucin in 10 of the 11 cases. The other case (one Ca) showed a small amount of thick mucin. In all cases, epithelial cells were identified, although cellularity was very low in four cases (three B and one Bo). Atypia was absent in two cases (two B) slight in two cases (two B), moderate in three cases (one Bo and two Ca), and severe in four cases (one Bo, one M, and two Ca). Mucinous epithelium was found in nine cases and nonmucinous epithelium in five cases (one Bo and four Ca). Papillary structures were observed in five cases (two Bo and three Ca), sheets in eight cases (four B, one Bo, one M, and two Ca), single atypical cells in five cases (one Bo and four Ca), irregular clusters in three cases (one Bo and two Ca), and nuclear grooves in two cases (one B and one Bo). CONCLUSIONS: The most common features of IPMT were extracellular mucin and sheets of mucinous epithelium. Papillae and nuclear grooves were not consistently found. Nonmucinous epithelium, severe atypia, single atypical cells, and irregular clusters indicated a high probability of malignant transformation. Even in the absence of atypia, a clinically significant diagnostic orientation can be established in most cases on the basis of the characteristic cytologic picture. 相似文献
105.
106.
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
107.
Caccamo N Meraviglia S La Mendola C Bosze S Hudecz F Ivanyi J Dieli F Salerno A 《European journal of immunology》2004,34(8):2220-2229
The 16-kDa protein of Mycobacterium tuberculosis represents an important antigenic target during bacillary latency and, consequently, should be considered as candidate subunit vaccine component. In this study, we have used CD4 T cell clones that recognize the peptide p91-110, an immunodominant and genetically permissive epitope, in the context of five different HLA-DR molecules and truncated and substituted variants of this peptide, to identify the minimal binding sequence (HLA-DR-binding core) and the minimal stimulatory sequence (TCR-binding core), as well as the residues that contact HLA-DR molecules and the TCR. We have found a common 9-mer sequence, spanning amino acids 93-101, as the binding core for HLA-DR1, -DR11, -DR13 and -DR7, but a longer (13-mer) sequence spanning amino acids 92-104 was required for binding to the HLA-DR15 molecules. F(93) was required for binding to all the tested HLA-DR molecules, hence allowing us to identify it as the N-terminal primary anchor residue (P1). Additionally, the binding requirements for other residues varied considerably between the tested alleles: A(94) for HLA-DR15, V(99) for HLA-DR1, -DR15, -DR11 and -DR7, R(100) for HLA-DR11 and -DR13, and L(104) for HLA-DR15. Concerning the residues of p91-110 peptide required for binding to the TCR, the pepscan analysis results would support the contention that P(-1) E(92), P6 F(98) would be important TCR contact sites because their substitutions led to full loss of T cell activation. Moreover, P8 R(100) is found to be critical residue in binding to HLA-DR11- and -DR13-restricted T cell clones, without influencing binding to the relevant HLA-DR molecule. Our results could be useful to design peptides with altered HLA anchor residues or TCR interaction sites to achieve remarkable increase in activity and to study their vaccine potential. 相似文献
108.
Biron-Shental T Fisch B Van Den Hurk R Felz C Feldberg D Abir R 《Fertility and sterility》2004,81(3):716-719
Ovarian follicles obtained from second and third-trimester human fetuses survived 4 weeks in organ culture and secreted 17-beta estradiol (E(2)). 相似文献
109.
110.