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61.
Mitotic disturbances and micronucleus induction in Syrian hamster embryo fibroblast cells caused by asbestos fibers.
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E Dopp J Saedler H Stopper D G Weiss D Schiffmann 《Environmental health perspectives》1995,103(3):268-271
Asbestos and other mineral fibers have long been known to induce lung cancer and mesothelioma. However, the primary mechanisms of fiber-induced carcinogenesis still remain unclear. We investigated the occurrence of mitotic disturbances induced by asbestos (amosite, crocidolite, chrysotile) in an in vitro approach using Syrian hamster embryo (SHE) fibroblast cells. The following endpoints were investigated: micronucleus formation as a result of mitotic disturbances and characterization of the induced micronucleus population by kinetochore staining and visualization of the spindle apparatus. Supravital UV-microscopy was used to analyze changes in interphase chromatin structure, impaired chromatid separation, and blocked cytokinesis. All three asbestos fiber types induced a high frequency of micronucleus formation in SHE cells (> 200/2000 cells) in a dose-dependent manner (0.1-5.0 micrograms/cm2), with a maximum between 48 hr and 66 hr exposure time. At higher concentrations (more than 5.0 micrograms/cm2) the micronucleus formation decreased again as a result of increased toxicity. Kinetochore staining of micronuclei revealed that 48 +/- 2% of asbestos-induced micronuclei reacted positively with CREST (antikinetochore) serum. Furthermore, spindle apparatus deformations occurred in cells with disturbed metaphases and anaphases, while the spindle fiber morphology appeared unchanged. Our results show that asbestos fibers may cause both loss and breakage of chromosomes in the absence of direct interaction with spindle fibers. 相似文献
62.
Sorbic acid, sodium sorbate and potassium sorbate were tested for their genotoxic potential in the Syrian hamster embryo (SHE) fibroblast micronucleus assay and the SHE cell transformation test in vitro. Sorbic acid and potassium sorbate showed no activity in either test system. When freshly prepared sodium sorbate solutions were used, no genotoxic or cell-transforming activity was detected. However, sodium sorbate as stored solution, which previously had been heated and sonicated to facilitate solubilization, yielded a positive response in both test systems. It is concluded that oxidation products of sodium sorbate that possess genotoxic and cell-transforming properties are formed under conditions of heating, sonication and storage. 相似文献
63.
BACKGROUND: An increasing incidence of systemic candidiasis has been reported in low birth weight infants requiring intensive care. We have retrospectively analyzed mucocutaneous Candida-colonization and infection rate in 422 preterm infants with a birthweight < 1,500 g. METHODS: All infants were treated at the NICU, University of G?ttingen, from 1/1985-5/1991. 359 neonates (85%) were on mechanical ventilation, no prophylactic antimycotic regimen was applied. Mucocutaneous swabs and cultures from various anatomic sites were regularly obtained from all infants. RESULTS: 37/422 preterm infants (8.8%) had mucocutaneous colonization with candida, none of our patients developed systemic candidiasis. In 7 mechanically ventilated patients (1.9%) Candida albicans or Candida tropicalis was repeatedly detected in the bronchial secretions; 1 patient who had invasive Candida-pneumonia was effectively treated with 5-Fluocytosin and Fluconazol. 4/352 (1.1%) central silastic catheters were colonized with Candida albicans; none of these patients required specific treatment. CONCLUSION: The low rate of mucocutaneous Candida-colonization and invasive infection found in our patients may be explained--at least in part--by epidemiological and obstetrical factor as well as by the procedures of the neonatal management. 相似文献
64.
Raphael Schiffmann Markus Ries Margaret Timmons John T Flaherty Roscoe O Brady 《Nephrology, dialysis, transplantation》2006,21(2):345-354
BACKGROUND: Fabry disease is an X-linked disorder of glycosphingolipid catabolism that is the result of an intracellular deficiency in the lysosomal enzyme alpha-galactosidase A (alpha-Gal A). This enzymatic defect results in the accumulation of globotriaosylceramide (Gb(3)) within cells and causes progressive neurological, cardiovascular and renal dysfunction. Our objective is to describe the safety and renal effects of long-term enzyme replacement therapy. METHODS: This was a single centre, prospective open-label treatment trial in 25 adult male Fabry patients who had completed a 6-month randomized placebo-controlled study and subsequently enrolled in an open-label extension study. Patients were treated every other week with agalsidase alfa (0.2 mg/kg) infused intravenously over 40 min. The main outcome measures were safety, antibody response and renal glomerular filtration rate (GFR). RESULTS: During the 4-4.5 years of enzyme replacement therapy, all eligible subjects were able to transition to home therapy. Eight patients developed persistent IgG antibodies to agalsidase alfa, but IgE antibodies were not detected in any patient. The development of IgG antibodies appeared not to affect any clinical end points. Estimated GFR remained stable in subgroups of patients with Stage I (GFR >90 ml/min) or Stage II (GFR 60-89 ml/min) chronic kidney disease at baseline. In contrast, in the subgroup of patients with Stage III chronic kidney disease (GFR 30-59 ml/min), the slope of the decline in GFR was reduced compared with comparable historical controls, suggesting that enzyme replacement therapy was slowing the decline of renal function in this susceptible population. CONCLUSIONS: Long-term enzyme replacement therapy with agalsidase alfa is safe and may slow the progressive decline in renal function that was commonly observed in adult males with Fabry disease. 相似文献
65.
66.
Transient neonatal hyperglycinemia 总被引:1,自引:0,他引:1
Two patients with neonatal seizures and subsequent normal neurological development were found to have nonketotic hyperglycinemia. In both patients, hyperglycinemia resolved at 6 weeks of age. After cerebrospinal fluid glycine levels were normalized, the seizures stopped completely in one child and were markedly improved in the other. The possible mechanisms for the hyperglycinemia are discussed. 相似文献
67.
In vivo release of non-neuronal acetylcholine from the human skin as measured by dermal microdialysis: effect of botulinum toxin
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Schlereth T Birklein F an Haack K Schiffmann S Kilbinger H Kirkpatrick CJ Wessler I 《British journal of pharmacology》2006,147(2):183-187
1.--Acetylcholine is synthesized in the majority of non-neuronal cells, for example in human skin. In the present experiments, the in vivo release of acetylcholine was measured by dermal microdialysis. 2.--Two microdialysis membranes were inserted intradermally at the medial shank of volunteers. Physiological saline containing 1 muM neostigmine was perfused at a constant rate of 4 microl min(-1) and the effluent was collected in six subsequent 20 min periods. Acetylcholine was measured by high-pressure liquid chromatography (HPLC) combined with bioreactors and electrochemical detection. 3.--Analysis of the effluent by HPLC showed an acetylcholine peak that disappeared, when the analytical column was packed with acetylcholine-specific esterase, confirming the presence of acetylcholine. 4.--In the absence of neostigmine, 71+/-51 pmol acetylcholine (n=4) was found during a 120 min period. The amount increased to 183+/-43 pmol (n=34), when the perfusion medium contained 1 microM neostigmine. 5.--Injection of 100 MU botulinum toxin subcutaneously blocked sweating completely, but the release of acetylcholine was not affected (botulinum toxin treated skin: 116+/-70 pmol acetylcholine/120 min; untreated skin: 50+/-20 pmol; n=4). 6.--Quinine (1 mM), inhibitor of organic cation transporters, and carnitine (0.1 mM), substrate of the Na(+)-dependent carnitine transporter OCTN2, tended to reduce acetylcholine release (by 40%, not significant). 7.--Our experiments demonstrate, for the first time, the in vivo release of non-neuronal acetylcholine in human skin. Organic cation transporters are not predominantly involved in the release of non-neuronal acetylcholine from the human skin. 相似文献
68.
Prust M Wang J Morizono H Messing A Brenner M Gordon E Hartka T Sokohl A Schiffmann R Gordish-Dressman H Albin R Amartino H Brockman K Dinopoulos A Dotti MT Fain D Fernandez R Ferreira J Fleming J Gill D Griebel M Heilstedt H Kaplan P Lewis D Nakagawa M Pedersen R Reddy A Sawaishi Y Schneider M Sherr E Takiyama Y Wakabayashi K Gorospe JR Vanderver A 《Neurology》2011,77(13):1287-1294
69.
Prall F Wöhlke M Klautke G Schiffmann L Fietkau R Barten M 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2006,114(3):201-210
Neoadjuvant radiation or chemoradiation is currently the treatment of choice for patients with locally advanced carcinoma of the rectum. To assess the effects of chemoradiation on tumour regression and on uninvolved mesorectal lymph nodes, a consecutive series of 76 patients receiving neoadjuvant chemoradiation and a stage-adapted control series of 57 patients without pretreatment were studied. Densities of cells positive for CD4 (T-helper cells), CD8 (cytotoxic T-cells), CD83 (mature dendritic cells), and CD57 (natural killer cells) were determined on immunostains. Tumour regression was graded, and presence or absence of extramural tumour was recorded. The densities of CD4+ T-lymphocytes and CD83+ dendritic cells in the paracortex of mesorectal lymph nodes were observed to be significantly reduced, as were the densities of CD57+ cells in the follicles; densities of CD8+ T-lymphocytes did not differ. Strong, moderate and poor tumour regression was observed in 29, 25, and 22 cases, respectively. For 12 patients, absence of extramural vital or regressing tumour was recorded, indicating pretherapeutic overstaging. The results bring to mind that neoadjuvant chemoradiation as a side effect may have a negative impact on anti-tumour immunity. Together with the drawback of overstaging the results argue for a careful selection of patients. 相似文献
70.