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Elizabeth Rosyold Russell Schilder Judy Walczak S. M. DiFino P. J. Flynn T. K. Banerjee W. J. Heim Paul E. Engstrom Robert F. Ozols Peter J. O'Dwyer 《Cancer chemotherapy and pharmacology》1992,29(4):305-308
Summary Phosphonacetyl-l-aspartate (PALA), an inhibitor of aspartate transcarbamylase that depletes uridine nucleotide pools, selectively potentiates the antitumor activity of 5-fluorouracil (5-FU) in preclinical models. Due to the promising results we obtained using PALA/5-FU in colorectal cancer, we performed a phase II trial in patients presenting with advanced pancreatic cancer. PALA was given intravenously at 250 mg/m2 on day 1, followed 24 h later by 2,600 mg/m2 5-FU given by 24-h infusion. Treatments were repeated weekly. A total of 41 patients who had not previously undergone chemotherapy were entered in the trial; of these, 35 were evaluable for response. Toxicity was generally mild to moderate; neurotoxicity (13/35) and diarrhea (8/35) predominated. Among the 35 patients, 1 achieved a complete response and 4, a partial remission, for an overall response rate of 14%. The median survival was 5.1 months. Pretreatment with PALA alone was not sufficient to enhance the activity of 5-FU in pancreatic cancer.Supported in part by grant CA 06927 from the National Cancer Institute 相似文献
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The Role of APO-1-Mediated Apoptosis in the Immune System 总被引:12,自引:0,他引:12
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APO-1(CD95)-dependent and -independent antigen receptor-induced apoptosis in human T and B cell lines 总被引:3,自引:0,他引:3
Peter Marcus E.; Dhein Jens; Ehret Andreas; Hellbardt Stefan; Walczak Henning; Moldenhauer Gerhard; Krammer Peter H. 《International immunology》1995,7(11):1873-1884
Certain B and T cell lines respond to activation signals, e.g.through the antigen receptor, by undergoing apoptotlc cell death.In T cells it has been recently shown that TCR-mediated apoptosisinvolves APO-1/Fas (CD95) receptor-ligand interaction. To investigatewhether the TCR-CD3 complex can trigger alternative apoptosispathways we generated subclones of the T cell line Jurkat whichwere completely resistant towards APO-1-mediated apoptosis.These JurkatR cells differed phenotypically from sensitive parentalJurkatS cells only by the lack of APO-1 protein expression.Although JurkatR cells responded normally to anti-CD3 stimulationby expression of APO-1 ligand they failed to undergo anti-CD3-inducedapoptosis. Thus, in Jurkat cells APO-1 -mediated apoptosis wasthe main, and might be the only, mechanism for anti-CD3-inducedcell death. However, BL-60 B cells, highly sensitive to anti-IgM-inducedapoptosis, did not use the APO-1 receptor-ligand system becausethey failed to express APO-1 ligand mRNA. Taken together, ourresults suggest that malignant T and B cell lines may use APO-1receptor-ligand-dependent and -independent antigen receptor-inducedapoptosis pathways respectively. Similarly, differential pathwaysmay be used by T and B cell subsets. 相似文献
5.
S C Bell R F James J A Jackson S R Patel G T Waites K Walczak 《American journal of reproductive immunology (New York, N.Y. : 1989)》1989,20(3):87-96
Monoclonal antibodies were raised against pregnancy-associated endometrial alpha 1-globulin (alpha 1-PEG), a 32 KD insulin-like growth factor binding protein (IGF-BP), which represents a major secretory product of the human decidualized endometrium during pregnancy. This class of IGF-BP has been implicated in the modulation of action, inhibitory and stimulatory, of insulin-like growth factors. Immunization with the protein purified from pregnancy endometrium resulted after myeloma fusion in the isolation of six hybridoma clones and the antibodies produced were characterized. The Ka of the antibodies ranged between 4.75 x 10(9) M-1 and 0.7 x 10(8) M-1. In Western blots all monoclonal antibodies reacted with purified protein of molecular weight 32 KD and specifically detected this IGF-BP species in culture medium and cytosolic extracts of pregnancy endometrium and amniotic fluid. The monoclonal antibodies appear to define three epitope-bearing regions as evidenced by their reactivity to polypeptide fragments of the protein. After synthesis and secretion by tissue explants in vitro the protein is susceptible to cleavage into fragments possessing different monoclonal antibody-defined reactivity. Employing immunohistochemical techniques the protein was principally localized to decidual cells in tissue sections of pregnancy endometrium and solely to these cells after enzymic digestion of the tissue. The implications of these results are discussed with respect to potential role of IGF-BP in the action of IGF upon the IGF-1 receptor-bearing populations, including lymphocytes and trophoblast cells, D in the decidua. 相似文献
6.
A phase II trial of temozolomide and IFN-alpha in patients with advanced renal cell carcinoma. 总被引:1,自引:0,他引:1
Usha Sunkara Janet R Walczak Lori Summerson Theresa Rogers Mario Eisenberger Samuel Denmeade Roberto Pili Carol Ann Huff Victoria Sinibaldi Michael A Carducci 《Journal of interferon & cytokine research》2004,24(1):37-41
The combination of temozolomide (TEM) and interferon-alpha (IFN-alpha) previously demonstrated a 30% response rate in metastatic melanoma. A single institution, phase II trial evaluating the efficacy of TEM/IFN in patients with advanced renal cell carcinoma (RCC) was conducted. Safety and tumor response were the main outcomes. Eligible patients received 200 mg/m(2)/day TEM orally on days 1-5 every 28 days, with IFN 2.5 million U/m(2)/day subcutaneously (s.c.) three alternate days/week for days 1-15 first cycle, then 5 million U/m(2)/day s.c. 3 alternate days/week throughout each 28-day cycle. Efficacy was evaluated every 8 weeks, and dose-limiting toxicities (DLTs) were treated with dose reductions of the culprit drug. Sixteen patients (ages 37-67) were initially enrolled. Of the 14 evaluable patients, there was one minor response. Best response was stable disease, with 7 patients remaining on study for > or =6 months. Five were alive for more than 2 years, and 2 remain alive at 45 and 50 months after enrollment. DLTs included TEM-induced myelosuppression and IFN-induced fever/chills. Other toxicities were mild to moderate (grades 1-3). The combination of TEM/IFN proved quite tolerable. This regimen appears inactive in terms of response in this population with poor prognosis, but the patients with stable disease > or =6 months remain of interest. 相似文献
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8.
Reduction of rapid eye movement sleep by diurnal and nocturnal seizures in temporal lobe epilepsy 总被引:12,自引:0,他引:12
BACKGROUND: Patients with brief, complex partial seizures frequently suffer from tiredness and decreased productivity that continue well beyond the postictal period. A possible explanation is that seizures, even when occurring during the day, disrupt sleep the following night. OBJECTIVE: To determine the effect of temporal lobe complex partial seizures on sleep structure and daytime drowsiness. METHODS: Patients with temporal lobe epilepsy were admitted for video-electroencephalography monitoring. All-night polysomnography was recorded under the following 3 conditions: seizure free, seizure during the day before the recording, and seizure during the recording. Percentage of time in each sleep stage, sleep efficiency, and time to first and second rapid eye movement (REM) period were compared for seizure vs control conditions. Daytime drowsiness was also measured, using a modified maintenance of wakefulness test and 2 subjective drowsiness tests. RESULTS: Daytime seizures reduced REM from 18%+/-1% to 12%+/-2% (P = .003). Night seizures reduced REM from 16%+/-1% to 6.8%+/-2% (P<.001). Night seizures also significantly reduced stages 2 and 4 while increasing stage 1 sleep. Night seizures, but not day seizures, significantly reduced sleep efficiency, increased time to first REM period, and increased drowsiness as measured by the maintenance of wakefulness test. CONCLUSIONS: Temporal lobe complex partial seizures decrease REM sleep, particularly when occurring during sleep but also when occurring on the previous day. This may, in part, be responsible for the prolonged impairment of functioning that some patients report following seizures. 相似文献
9.
Walczak S 《Journal of medical systems》2000,24(1):29-37
Medical practitioners are under ever increasing pressure to maximize patient care, while minimizing costs. One productivity area that has not previously undergone thorough investigation is the efficient utilization of time for intra-office communication. Medical office personnel typically need to communicate patient information and resource requests, as well as personal messages. An intra-office communication system is designed that reduces time-waste typically incurred in medical office environments. Redesigning medical offices with intra-office communication systems provides time savings of several man hours per day. The subsequent increase in time efficiency enables higher quality of patient care and larger patient loads to be managed by existing medical staff. 相似文献
10.
Xiang Li Chun-Hao Huang Francisco J. Snchez-Rivera Margaret C. Kennedy Darjus F. Tschaharganeh John P. Morris IV Antonella Montinaro Kevin P. O'Rourke Ana Banito John E. Wilkinson Chi-Chao Chen Yu-Jui Ho Lukas E. Dow Sha Tian Wei Luan Elisa de Stanchina Tinghu Zhang Nathanael S. Gray Henning Walczak Scott W. Lowe 《Proceedings of the National Academy of Sciences of the United States of America》2022,119(17)