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51.
Antisense RNA-mediated reduction of p53 induces malignant phenotype in nontumorigenic rat urothelial cells 总被引:2,自引:1,他引:2
p53 mutation is commonly associated with high-grade, high-stage human
urothelial carcinomas. Recent studies suggest that p53 mutation in low-
grade, low-stage bladder carcinomas may be correlated with the progression
of the disease. In the present study, we used antisense RNA methodology in
vitro to evaluate the significance of the loss of p53 function at an early
stage of urinary bladder carcinogenesis. An immortalized nontumorigenic rat
urothelial cell line (MYP3) that strongly expresses wild-type (WT) p53 was
transfected with a plasmid (pcDL-SR alpha-296) containing a rat WT p53 cDNA
in antisense orientation. The transfection resulted in a significant
reduction in p53 mRNA expression and protein synthesis, in stimulation of
anchorage- dependent growth, and in acquisition of anchorage-independent
growth potential. Three such clones, when tested in athymic nude mice, all
formed muscle-invasive, high-grade transitional cell carcinomas at s.c.
injection sites. When cells were inoculated into an orthotopic site
(urinary bladder), one of two antisense transfectants tested formed bulky
tumors in the bladder in all seven nude mice and metastases to lungs in
three of the seven mice. Analysis of these cells revealed a decrease in the
expression of p21 (WAF1, sdi1, or CIP1) and retinoblastoma (Rb) gene
product. Phosphorylation of Rb protein was not inhibited when the cells
were starved. No significant difference was observed in the expression of
p16 protein. In cell cycle analysis, all antisense transfectants tested
escaped from G1 arrest by starvation. Furthermore, secretion of interleukin
(IL)-6 into culture medium was increased significantly. Treatment with
anti-IL-6 antibody suppressed anchorage-dependent growth. This study
directly demonstrates that the loss of p53 function at an early stage of
urothelial carcinogenesis may result in acquisition of a malignant
phenotype by regulating IL-6 production as well as cell cycle related
genes.
相似文献
52.
In the present study, we examined the actions of the NMDA antagonist dizocilpine (MK801) on electrically evoked release and uptake of noradrenaline (NA) in the locus coeruleus (LC), serotonin (5-HT) in the dorsal raphe nucleus (DRN) and dopamine (DA) in the nucleus accumbens (NAc), measured by fast cyclic voltammetry (FCV) in rat brain slices. Dizocilpine (10 microM) significantly increased NA (to 248 +/- 15%) and 5-HT release (to 184 +/- 29%) and slowed monoamine uptake in the LC (t1/2 = 853 +/- 129%) and the DRN (t1/2 = 387 +/- 70%), respectively. However, dizocilpine had no effect on DA release or uptake in NAc. Actions on monoamines are thus likely and should be considered in the interpretation of data regarding dizocilpine. 相似文献
53.
血、尿中安眠酮及其代谢物的测定 总被引:1,自引:0,他引:1
通过一例安眠酮中毒病人血、尿中安眠酮及其代谢物的测定,描述了用紫外光谱(uv)、气相色谱(GC)和气相色谱质谱(GC/MS)法测定安眠酮及其代谢物的系统分析方法。样品的提取净化采用液一液萃取和固相萃取两种方法,都得到了很好的结果。紫外光谱用于测定血、尿中安眠酮和其代谢物的总量;气相色谱用于测定血、尿中安眠酮原药的含量;气相色谱质谱则用于鉴定血、尿中的安眠酮及其代谢物。除安眠酮外,血、尿中共检出10种安眠酮代谢物,其中包括两种乙酰化代谢物。此法还为临床救治提供指导。 相似文献
54.
R Pettengell C Donatti P Hoskin C Poynton P J Kettle B Hancock S Johnson M J S Dyer S Rule M Walker D Wild 《Annals of oncology》2008,19(3):570-576
BACKGROUND: The purpose of this study was to determine whether there was a relationship between disease activity and health functioning, as measured by a range of patient-reported outcome (PRO) measures in patients with follicular lymphoma (FL). PATIENTS AND METHODS: A total of 222 patients with FL were recruited from eight sites across the UK and they completed a number of PRO measures. The participants were analyzed across five disease states: 'active disease-newly diagnosed', 'active disease-relapsed', 'partial response', 'complete response' and 'disease free'. The relationship between these disease states and their level of health functioning was assessed as well as the relationship between being 'on' or 'off' chemotherapy and disease state. RESULTS: In terms of health-related quality of life (HRQoL), participants in the relapsed category had the lowest mean physical well-being, emotional well-being, functional well-being and social well-being score. In a regression analysis, the 'active disease-relapsed' group acted as a significant predictor for each PRO variable. In addition, the remission group acted as a significant predictor of high anxiety scores as measured by the Hospital Anxiety and Depression Scale. CONCLUSION: The results of this study demonstrate that various aspects of patient-reported health outcomes differ according to disease state in patients with FL. For those patients who have relapsed, they are more likely to experience worse HRQoL and other patient-reported health outcomes than patients newly diagnosed, in partial or complete remission or when completely disease free. 相似文献
55.
OBJECTIVE: To evaluate the need for initial inpatient treatment for patients being treated with low-dose intramuscular methotrexate for low-risk gestational trophoblastic neoplasia (GTN). STUDY DESIGN: Clinical notes of all patients treated with low-dose intramuscular methotrexate for low-risk GTN were analyzed and side effects noted. RESULTS: There were no episodes of increased uterine bleeding requiring extra medical intervention. There were 7 cases of chest pain; none required a change from methotrexate chemotherapy. CONCLUSION: Patients being treated with low-dose intramuscular methotrexate for low-risk GTN do not need to be treated routinely in the hospital for their first treatment cycle. 相似文献
56.
Franklin Hollander Albert Cornell Henry Doubilet M. Feldman Charles A. Flood M. H. F. Friedman J. Duffy Hancock Thomas A. Johnson Allen A. Jones N. W. Jones J. Kenneth Karr Morris Kesilman Henry H. Lerner Philip Levitsky Jesshill Love Franz J. Lust B. B. Vincent Lyon Ira A. Manville Arthur E. Meyer H. Necheles Frank Neuwelt Sam Overstreet J. F. Pessel C. Graham Reid Maurice Rothman David J. Sandweiss R. Schindler Harry Shay Virgil E. Simpson H. J. Sims Henry Tumen Robert Turell Edgar Wayburn Dwight Wilbur John H. Willard 《The American journal of digestive diseases》1940,7(12):542-542
57.
BACKGROUND: Recent experimental data indicate that the targeting of the costimulatory molecule CD40-ligand (CD154) may well offer an opportunity for tolerance induction in transplant recipients and patients with autoimmune diseases, although the optimal therapeutic strategy for clinical application of CD154 monoclonal antibody (mAb) is unclear. METHODS: We undertook vascularized heterotopic cardiac allograft transplantation in completely MHC-mismatched mice, treated recipients with CD154 mAb plus various immunosuppressive agents, and performed flow cytometric analysis of CD154 expression by T cells activated in vitro in the presence of corresponding immunosuppressive agents. We also tested the extent to which CD154 induction was NFkappaB-dependent by using NFkappaB/p50-deficient mice as allograft recipients and as source of cells for in vitro studies of CD154 induction, and through use of proteasome inhibitors to block IkappaBalpha degradation and NFKB activation in wild-type mice. RESULTS: Concomitant use of cyclosporin A or methylprednisolone, but not rapamycin or mycophenolate, inhibited CD154 mAb-induced allograft survival. The differential effects of these agents on CD154 mAb-induced tolerance correlated with their capacity to inhibit activation-induced CD154 expression on CD4+ T cells. Full expression of CD154 expression was found to require NF-kappaB activation, and CD154 mAb was ineffective in NF-kappaB/p50 deficient allograft recipients or control mice in which NF-kappaB activation was blocked by proteasome inhibition. CONCLUSIONS: Strategies to use CD154 mAb clinically must take into account the effects of immunosuppressive agents on CD154 induction, which seems to be at least partially NF-kappaB dependent. Our data suggest that ligation of surface-expressed CD154 provides an important signal that modulates T cell activation and thereby contributes to the effects of CD154 mAb, in addition to previously recognized actions involving blockade of CD40/CD154-dependent cell activation and activation-induced cell death. 相似文献
58.
59.
60.
Grant Rutherford Marcia R Friesen Robert D McLeod 《Online Journal of Public Health Informatics》2012,4(3)
This work uses agent-based modelling (ABM) to simulate sexually transmitted infection (STIs) spread within a population of 1000 agents over a 10-year period, as a preliminary investigation of the suitability of ABM methodology to simulate STI spread. The work contrasts compartmentalized mathematical models that fail to account for individual agents, and ABMs commonly applied to simulate the spread of respiratory infections. The model was developed in C++ using the Boost 1.47.0 libraries for the normal distribution and OpenGL for visualization. Sixteen agent parameters interact individually and in combination to govern agent profiles and behaviours relative to infection probabilities. The simulation results provide qualitative comparisons of STI mitigation strategies, including the impact of condom use, promiscuity, the form of the friend network, and mandatory STI testing. Individual and population-wide impacts were explored, with individual risk being impacted much more dramatically by population-level behaviour changes as compared to individual behaviour changes. 相似文献