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31.
Neil E Martin Thomas B Brunner Krystina D Kiel Thomas F DeLaney William F Regine Mohammed Mohiuddin Ernest F Rosato Daniel G Haller James P Stevenson Debbie Smith Barnali Pramanik Joel Tepper Wesley K Tanaka Briggs Morrison Paul Deutsch Anjali K Gupta Ruth J Muschel W Gillies McKenna Eric J Bernhard Stephen M Hahn 《Clinical cancer research》2004,10(16):5447-5454
PURPOSE: Preclinical and clinical studies have demonstrated that inhibition of prenylation can radiosensitize cell lines with activation of Ras and produce clinical response in patients with cancer. The aim of this study was to determine the maximally tolerated dose of the dual farnesyltransferase and geranylgeranyltransferase I inhibitor L-778,123 in combination with radiotherapy for patients with locally advanced pancreatic cancer. EXPERIMENTAL DESIGN: L-778,123 was given by continuous intravenous infusion with concomitant radiotherapy to 59.4 Gy in standard fractions. Two L-778,123 dose levels were tested: 280 mg/m2/day over weeks 1, 2, 4, and 5 for dose level 1; and 560 mg/m2/day over weeks 1, 2, 4, 5, and 7 for dose level 2. RESULTS: There were no dose-limiting toxicities observed in the eight patients treated on dose level 1. Two of the four patients on dose level 2 experienced dose-limiting toxicities consisting of grade 3 diarrhea in one case and grade 3 gastrointestinal hemorrhage associated with grade 3 thrombocytopenia and neutropenia in the other case. Other common toxicities were mild neutropenia, dehydration, hyperglycemia, and nausea/vomiting. One patient on dose level 1 showed a partial response of 6 months in duration. Both reversible inhibition of HDJ2 farnesylation and radiosensitization of a study patient-derived cell line were demonstrated in the presence of L-778,123. K-RAS mutations were found in three of the four patients evaluated. CONCLUSIONS: The combination of L-778,123 and radiotherapy at dose level 1 showed acceptable toxicity in patients with locally advanced pancreatic cancer. Radiosensitization of a patient-derived pancreatic cancer cell line was observed. 相似文献
32.
MJ Stevens PD Stricker J Saalfeld PC Brenner R Kooner GFA O'Neill PJ Duval RS Jagavkar P Cross J Martland 《Journal of Medical Imaging and Radiation Oncology》2003,47(2):152-160
Combination high dose rate brachytherapy (HDRB) and external beam radiation therapy is technically and clinically feasible as definitive treatment for localized prostate cancer. We report the first large Australian experience using this technique of radiation dose escalation in 82 patients with intermediate‐ and high‐risk disease. With a median follow up of 3 years (156 weeks), complications were low and overall prostate‐specific antigen progression‐free survival was 91% using the American Society for Therapeutic Radiology and Oncology consensus definition. The delivery of hypofractionated radiation through the HDRB component shortens overall treatment time and is both biologically and logistically advantageous. As a radiation boost strategy, HDRB is easy to learn and could be introduced into most facilities with brachytherapy capability. 相似文献
33.
Screening for complement deficiency in bacterial meningitis 总被引:1,自引:0,他引:1
T Ernst PJ Späth C Aebi UB Schaad MG Bianchetti 《Acta paediatrica (Oslo, Norway : 1992)》1997,86(9):1009-1010
Seventy-seven children with bacterial meningitis were screened for complement deficiency. Both the classical and the alternate pathways were normal in 75 patients. Transiently reduced total haemolytic activity of the classical pathway was documented in a boy with meningococcal meningitis. Total haemolytic activity of both the classical and the alternate pathways were reduced in another patient with pneumococcal meningitis: individual complement components determination indicated predominant activation of the alternate pathway. 相似文献
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The major burden of preterm birth is in the developing world, where most of the increasing death and morbidity is secondary to infectious diseases such as malaria, HIV, tuberculosis, bacterial vaginosis and intestinal parasites. In some developing countries, the growth of medical care has outstripped the growth of preventive public health, with an associated increase in iatrogenic preterm births. In developed countries, more than one-third of preterm births are medically indicated because of conditions such as fulminating pre-eclampsia or severe intrauterine growth restriction. Neither of these conditions is currently preventable. One in five preterm births is associated with multiple pregnancy, and these have been greatly increased by assisted reproduction techniques. The use of tocolytics has proved disappointing perhaps because inflammation rather than spontaneous uterine activity is increasingly recognised as the final common pathway. Inappropriate antibiotics used late in pregnancy are ineffective and may have adverse effects. Currently, the most promising interventions are public health related and include reducing the transmission of communicable diseases, improvements in the management of diabetes and reduction in harmful behaviours such as smoking and drug abuse. 相似文献
38.
The bioavailability of two different tablet formulations of tamoxifen was studied in twelve healthy male volunteers. Two tablets, each of 10 mg, of both preparations were administered orally at intervals of two weeks in a randomized cross-over design. Samples of blood for tamoxifen measurement were taken for up to 48 h following administration. Tamoxifen was measured by an HPLC method sensitive to 2.0 ng ml(-1). The area under the concentration-time curve was similar for both preparations. The study, therefore, did not demonstrate any differences between the bioavailability of the two preparations of tamoxifen. 相似文献
39.
John F. Briggs Morris Fishbein Morris Fishbein Morris Fishbein Morris Fishbein 《Postgraduate medicine》2013,125(3):307-310
Abandonment of the classic radical mastectomy is not warranted at present. Excision of the internal mammary nodes can be defended in cases in which the cancer is situated in the medial or central part of the breast, with the recognition that it is experimental. Controlled cooperative trials would do much to answer the unsolved questions regarding the care of patients with breast cancer. 相似文献
40.
AbstractIntravenous immunoglobulin (IGIV) replacement therapy is the standard of care for primary immunodeficiencies with impaired humoral immunity. It is also the immunomodulatory therapy of choice for some types of neuroimmunologic and autoimmune hematologic disorders and for immunomodulation in bone marrow and some solid organ transplants. Currently available IGIV products include older lyophilized formulations, 5% liquid products, and newer, liquid, ready-to-use, 10% formulations. Differences in the formulations, manufacturing processes, excipients, pH, and other physicochemical properties of IGIV products may affect their clinical efficacy and tolerability. Among at-risk patients, the possibility of serious complications such as renal insufficiency, heart failure, thrombotic events, and immunological reactions may be increased if an IGIV formulation has sugar as a stabilizer, has high sodium or immunoglobulin A (IgA) content, or is hyperosmolar. The 10% liquid formulations may offer advantages because of their lower IgA concentrations, optimal pH, glycine or proline stabilizers, low sodium content, and lower osmolality. Liquid formulations are more convenient for patients and health care providers due to shorter infusion times and easier preparation and administration. 相似文献