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71.
G. Fegiz M.D. M. Di Paola M.D. L. Angelini M.D. A. Bertolotti M.D. S. Colizza M.D. 《World journal of surgery》1977,1(3):343-345
Lymphocytic infiltration in and around the tumor together with sinus histiocytosis and follicular hyperplasia in regional nodes has been studied in a group of 310 patients with breast cancer treated by standard radical mastectomy. The semiquantitative grading of these particular changes made possible the division of patients into 3 classes of putative host resistance, namely, no or poor reaction, good reaction, and strong reaction. The grading was shown to have a close correlation with prognosis both 5 and 10 years after surgery. More interestingly, the incidence of metastases in the 3 classes was significantly different, i.e. much higher in the non-responder group, thus supporting the hypothesis that prognosis in breast cancer is closely related to a histological picture of cell-mediated immunity against the tumor, and that this resistance probably acts as a local barrier to the diffusion of the tumor.
Résume Chez 310 malades atteintes de cancer du sein et traitées par mastectomie radicale, nous avons étudié l'infiltration lymphocytaire intra- et péritumorale et, dans les ganglions régionaux, l'histiocytose sinusale et l'hyperplasie folliculaire. Par une gradation semiquantitative, les malades ont été divisées en trois groupes de résistance potentielle: pas ou peu de réaction, réaction d'intensité moyenne, forte réaction. Cette gradation est en bonne corrélation avec le pronostic à 5 et 10 ans. De plus, la fréquence des métastases diffère dans les trois groupes; elle est beaucoup plus élevée dans le groupe à réaction nulle ou faible. Ces données confirment l'hypothèse qui admet que le pronostic du cancer du sein est en relation avec les aspects histologiques d'immunité cellulaire antitumorale et que celle-ci agit vraisemblablement comme un barrage local s'opposant à la diffusion de la tumeur.相似文献
72.
Carnuccio P Assenza M Lombardi A Santagati A Romagnoli F Di Paola M 《Il Giornale di chirurgia》2000,21(8-9):323-326
Cardiac complications are the main cause of perioperative mortality. A preoperative electrocardiogram and cardiologist's consultation are usually performed to get information about cardiac state of patients undergoing surgery and to prevent complications. In their study the Authors applied to 1715 patients undergoing surgery an evaluation schedule for the cardiac surgical risk, including an ECG as first-level test, performed systematically on the whole sample. The aim was to assess predictive value of this preoperative examination to verify its efficacy as routine test. Basing on results achieved, electrocardiogram is not routinely indicated before noncardiac elective surgery, but it should be requested for the patients having high risk of cardiac complications at an accurate clinical-anamnestic examination. Therefore, clinical judgement, that is the first level of any preoperative evaluation, should be the basis for ordering an ECG to be considered a second-level test. 相似文献
73.
Wainer Zoli Luca Ricotti Anna Tesei Paola Ulivi Anna Gasperi Campani Francesco Fabbri Roberta Gunelli Giovanni Luca Frassineti Dino Amadori 《Clinical cancer research》2004,10(4):1500-1507
PURPOSE: The aim of the study was to evaluate the activity of epidoxorubicin (EPI) and gemcitabine (GEM) and to define the most effective schedule in human bladder cancer cells. EXPERIMENTAL DESIGN: The study was performed on HT1376 and MCR cell lines. Cells were exposed for 1 and 24 h to drugs used in different schemes. Cytotoxic activity was evaluated by the sulforhodamine B assay, potential clinical activity was estimated by relative antitumor activity, and the type of drug interaction was assessed using the method of Chou and Talalay. Cell cycle perturbations and apoptosis were assessed by flow cytometry; BAX, BCL-2, and P53 expression was evaluated by Western blot; and DNA damage was assessed using the alkaline Comet assay. RESULTS: EPI and GEM produced a cytotoxic effect in both cell lines, with 50% inhibitory concentration and relative antitumor activity values suggestive of a high clinical activity. Simultaneous treatment with EPI and GEM and the sequence GEM-->EPI caused an antagonistic interaction (combination index > 1) after both 1- and 24-h treatments. Conversely, the inverse sequence, EPI-->GEM, produced a synergistic interaction that was more pronounced in MCR cells than in HT1376 cells. The increase in DNA-damaged cells from 10% to 20% after single-drug exposure to 40-60% at the end of EPI-->GEM treatment may explain the synergistic interaction produced by the anthracycline-antimetabolite sequence. CONCLUSIONS: Our findings show that the efficacy of the EPI and GEM combination is highly schedule dependent and indicate that the most active scheme is EPI followed by GEM, which is currently being validated in an ongoing intravesical Phase I-II clinical protocol. 相似文献
74.
75.
Hans Gelderblom Ramon Salazar Jaap Verweij George Pentheroudakis Maja J A de Jonge Martin Devlin Christel van Hooije Francis Seguy Rosendo Obach Joan Pru?onosa Paola Principe Chris Twelves 《Clinical cancer research》2003,9(11):4101-4107
PURPOSE: Diflomotecan (BN80915) is an E-ring modified camptothecin analogue that possesses greater lactone stability in plasma compared with other topoisomerase I inhibitors, a potential advantage for antitumor activity. As with other camptothecins, oral administration has pharmacological and clinical advantages. This Phase I study was performed to assess the feasibility of the administration of oral diflomotecan, to determine the maximum-tolerated, dose its bioavailability, and to explore the pharmacokinetics. EXPERIMENTAL DESIGN: An initial i.v. bolus was administered to assess the bioavailability of diflomotecan. Fourteen days later, diflomotecan was administered p.o. once daily for 5 days to adult patients with solid malignant tumors and repeated every 3 weeks. BN80915 and its open lactone form BN80942 were measured. RESULTS: Twenty-two patients entered the study and received a total of 57 cycles of oral diflomotecan at flat dose levels of 0.10, 0.20, 0.27, and 0.35 mg. The main toxicity was hematological, but some patients experienced alopecia, mild gastrointestinal toxicity, and fatigue. At the 0.35-mg dose level, 2 of 4 patients experienced dose-limiting toxicity comprising grade 3 thrombocytopenia with epistaxis and febrile neutropenia in 1 patient and uncomplicated grade 4 neutropenia lasting for >7 days in another. Toxicity was acceptable at the 0.27-mg dose level at which dose-limiting toxicities were observed in 3 of 12 patients (grade 4 neutropenia > 7 days, complicated by fever in 1 patient but without other signs of infection). After two cycles of diflomotecan, 6 patients had disease stabilization, which was maintained in 2 patients for 9 months and >1 year, respectively. Diflomotecan pharmacokinetics were linear over the dose range studied. Systemic exposure correlated with the fall in WBC counts. The mean oral bioavailability (+/-SD) was 72.24 +/- 59.2% across all dose levels. Urinary excretion of BN80915 was very low. CONCLUSIONS: The recommended oral diflomotecan dose for Phase II studies is 0.27 mg/day x 5 every 3 weeks. This regimen is convenient and generally well tolerated with a favorable pharmacokinetic profile and high but variable bioavailability. 相似文献
76.
p73 Expression in human normal and tumor tissues: loss of p73alpha expression is associated with tumor progression in bladder cancer. 总被引:1,自引:0,他引:1
77.
Antonio Macciò M.D. Paola Lai M.D. Maria Cristina Santona M.D. Loredana Pagliara M.D. Gian Benedetto Melis M.D. Giovanni Mantovani M.D. 《Gynecologic oncology》1998,69(3):248-252
The serum levels of interleukin-(IL-)1α, IL-1β, IL-2, IL-6, TNFα, and sIL-2R and the proliferative response of peripheral blood mononuclear cells (PBMC) to phytohemagglutinin (PHA), anti-CD3 monoclonal antibody (mAb), recombinant IL-2 (rIL-2), and the combination of PHA or anti-CD3 mAb with rIL-2 were studied and correlated with serum levels of C-reactive protein (CRP) in women with advanced epithelial ovarian cancer. The expression of CD25 and CD122 subunities of membrane-bound IL-2R on PHA- or anti-CD3 mAb-stimulated PBMC was also studied. In comparisons with the controls, PBMC response to PHA, anti-CD3 mAb, and rIL-2 was significantly lower in the cancer patients. The addition of exogenous rIL-2 to the PBMC cultures increased response in both controls and patients but did not modify the significance of the differences. After stimulation with PHA or anti-CD3 mAb, the percentage of PBMC CD25+or CD122+was significantly lower in patients. The serum levels of IL-1α, IL-1β, IL-6, TNFα, sIL-2R, and CRP were significantly increased in patients compared to the controls. Instead, no differences were observed for serum levels of IL-2. A strong association was found between high serum levels of the above-mentioned cytokines, sIL-2R, and CRP. The results of our study on advanced stage (IIIb–IV) ovarian cancer patients are consistent with the previously reported hypothesis that high IL-6 and/or CRP serum levels may represent an important and independent prognostic factor of the likely outcome in cancer patients. 相似文献
78.
Aldo Becciolini Manuela Balzi Paola Faraoni Elena Tisti Giorgia Zappoli Thyrion Valentino Giach Luca Bandettini Christopher S. Potten 《Acta oncologica (Stockholm, Sweden)》1998,37(1):65-71
Cell kinetics parameters have been analysed in colonic mucosa at different distances from a tumour in patients with colon carcinoma. Total cell number (TCN), H thymidine labelling index (TLI), mitotic index (MI), Goblet cell index (GCI) and the distribution of labelled cells along the crypt column (cell position frequency plot) were determined in well-aligned crypts. Total cell number, GCI and the labelled cell position frequency plots were similar in different samples from the same individual. A negative linear correlation between TCN and TLI was observed. The analysis of the cell position plots showed two patterns 1) with a high concentration in the bottom fifth of the crypt and 2) with frequent labelled cells at high positions. Whereas a negative correlation between overall TLI and the percent contribution to the TLI of the lowermost fifth was seen, the correlation was positive for the next 3 fifths and labelling was absent in the last part of the crypt. 相似文献
79.
Riccardo Dolcetti Paola Zancai Roberta Cariati Mauro Boiocchi 《Leukemia & lymphoma》1998,29(3):269-281
Retinoids have been shown to be effective in the chemoprevention and treatment of certain human malignancies. In this review, we will summarize our recent results concerning the effects of retinoids on the proliferation and differentiation of Epstein-Barr virus (EBV)-immortalized lymphoblastoid B-cell lines (LCLs), an in vitro model of EBV-related lymphoproliferative disorders arising in immunosuppressed hosts. Retinoids proved to be powerful inhibitors of the proliferation of EBV-infected LCLs in vitro, with 13-cis-retinoic acid (RA), all-trans-RA, and 9-cis-RA being the most effective compounds. Of note, retinoid-induced growth arrest in vitro appears irreversible at drug concentrations (10--6 mol/L) which may be reached in man after oral systemic therapy. The antiproliferative activity exerted by retinoids on LCLs is a generalized phenomenon usually associated with a progressive accumulation in G0/G1 phases of treated cells. The strong upregulation of p27Kipl invariably observed in cells exposed to retinoids may contribute to the decreased number of cycling cells, probably by inhibiting the transition from the G1 to S phase. Moreover, we obtained evidence indicating that the antiproliferative effects of retinoids are not dependent on the induction of terminal differentiation of EBV-immortalized B lymphocytes. In fact, the modifications induced by retinoids relative to LCL morphology, phenotype (downregulation of CD19, HLA-DR, and s-Ig, and upregulation of CD38 and c-Ig), and IgM production were highly variable among the lines tested and often only slightly relevant. Finally, the antiproliferative activity exerted by retinoids on LCLs is not mediated by a direct modulation of viral latent antigens, since EBNA-2 and LMP-1 downregulation was a late event detected only in some cell lines. These results indicate that retinoids may be useful in the medical treatment of EBV-related lymphoproliferative disorders of immunosuppressed patients, particularly in the earlier phases of these diseases. 相似文献
80.
In vitro and in vivo interaction between cisplatin and topotecan in ovarian carcinoma systems 总被引:7,自引:0,他引:7
Simona Romanelli Paola Perego Graziella Pratesi Nives Carenini Monica Tortoreto Franco Zunino 《Cancer chemotherapy and pharmacology》1998,41(5):385-390
Topotecan, a camptothecin analogue, is a␣specific inhibitor of topoisomerase I approved for use in the treatment of patients
with refractory ovarian carcinoma. The drug's mechanism of action suggests a potential efficacy of drug combinations incorporating
DNA-damaging agents. In an attempt better to define a␣rational basis for drug combination we examined the effect of topotecan
on the cytotoxicity and antitumor activity of cisplatin in an ovarian carcinoma system growing in vitro and in vivo as a tumor
xenograft. The in vitro cell system included a cisplatin-sensitive cell line, IGROV-1, and a cisplatin-resistant subline,
IGROV-1/Pt0.5, which is characterized by p53 mutation and loss of normal function of the wild-type gene of the parental cell
line. This cell system was chosen since the cell sensitivity to DNA-damaging agents appears to be dependent on p53 gene status.
Cytotoxicity was assessed by the growth inhibition assay using different schedules: (a) a 1-h period of cisplatin exposure
followed by a 24-h topotecan treatment and (b) a 1-h period of simultaneous exposure to cisplatin and topotecan. In the case
of the sequential schedule, an additive interaction was observed in IGROV-1 and IGROV-1/Pt0.5 cells. When the simultaneous
schedule was used, a synergistic interaction, more evident for the cisplatin-sensitive cells, was found. On the basis of these
observations at a cellular level, the effect of concomitant administration of the two drugs (i.e., the most favorable schedule)
was studied in the IGROV-1 tumor xenograft, which is moderately responsive to cisplatin and topotecan. Suboptimal doses of
each drug (with a low dose of topotecan, 5.1 mg/kg) achieved an antitumor effect comparable with or superior to that of the
optimal dose of a single treatment (tumor weight inhibition, 60%), thus indicating a␣pharmacological advantage of the combination
over the single treatment. However, an increase in the topotecan dose (7.1 mg/kg) was associated with an evident increase
in the toxicity of the combination, thereby suggesting that the drug interaction was not tumor-specific. Although the molecular
basis of the drug interaction is not clear, it is likely that inhibition of topoisomerase I affects the ability of cells to
repair cisplatin adducts. Such findings may have pharmacological implications since they suggest the potential clinical interest
of topoisomerase I inhibitors in combination with cisplatin.
Received: 14 June 1997 / Accepted: 18 September 1997 相似文献