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51.
Dina Chelouche Lev Amir Onn Vladislava O Melinkova Claudia Miller Valerie Stone Maribelis Ruiz Eric C McGary Honnavara N Ananthaswamy Janet E Price Menashe Bar-Eli 《Journal of clinical oncology》2004,22(11):2092-2100
PURPOSE: In recent years, the incidence of cutaneous melanoma has increased more than that of any other cancer. Dacarbazine is considered the gold standard for treatment, having a response rate of 15% to 20%, but most responses are not sustained. Previously, we have shown that short exposure of primary cutaneous melanoma cells to dacarbazine resulted in the upregulation of interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF). The purpose of the present study was to determine how long-term exposure of melanoma cells to dacarbazine would affect their tumorigenic and metastatic potential in vivo. MATERIALS AND METHODS: The primary cutaneous melanoma cell lines SB2 and MeWo were repeatedly exposed in vitro to increasing concentrations of dacarbazine, and dacarbazine-resistant cell lines SB2-D and MeWo-D were selected and examined for their ability to grow and metastasize in nude mice. RESULTS: The dacarbazine-resistant cell lines SB2-D and MeWo-D exhibited increased tumor growth and metastatic behavior in vivo. This increase could be explained by the activation of RAF, MEK, and ERK, which led to the upregulation of IL-8 and VEGF. More IL-8, VEGF, matrix metalloproteinase-2 (MMP-2), and microvessel density (CD-31) were found in tumors produced by SB2-D and MeWo-D in vivo than in those produced by their parental counterparts. No mutations were observed in BRAF. CONCLUSION: Our results have significant clinical implications. Treatment of melanoma patients with dacarbazine could select for a more aggressive melanoma phenotype. We propose that combination treatment with anti-VEGF/IL-8 or MEK inhibitors may potentiate the therapeutic effects of dacarbazine. 相似文献
52.
Amir Onn Takeshi Isobe Wenjuan Wu Satoshi Itasaka Tomoaki Shintani Keiko Shibuya Yokoi Kenji Michael S O'reilly Isaiah J Fidler Roy S Herbst 《Clinical cancer research》2004,10(24):8613-8619
PURPOSE: The purpose is to evaluate whether inhibition of epidermal growth factor receptor (EGFR) activation by PKI166, an EGFR-tyrosine kinase inhibitor, affects growth of human lung cancer implanted orthotopically into the lungs of nude mice. EXPERIMENTAL DESIGN: Lungs of mice were injected with NCI-H358 human bronchioloalveolar cancer cells. In three experiments, groups of mice (n = 10 per group) were randomized 7 days after tumor implantation to receive one of the following treatments: i.p. paclitaxel 100 or 200 microg (4 or 8 mg/kg) once per week, oral PKI166 100 or 200 mg/kg three times per week, paclitaxel plus PKI166, or i.p. saline and oral PKI166-vehicle (control) for 5 weeks. Mice were killed 6.5 to 8 weeks after tumor implantation. The experiments were repeated with PC14PE6 human lung adenocarcinoma cells to assess effect on survival. RESULTS: Immunohistochemical analyses revealed the expression and phosphorylation of EGFR in the growing tumors. Treatment with PKI166 alone or in combination with paclitaxel diminished activation of EGFR on tumor cells, yet maximal therapeutic effect was observed in mice treated with paclitaxel alone. Activated mitogen-activated protein kinase and basic fibroblast growth factor expression were similar in all treatment groups. Survival in mice treated with the combination of paclitaxel and PKI166 was shorter than in those treated with paclitaxel alone. CONCLUSIONS: Our results suggest that concurrent administration of EGFR-tyrosine kinase inhibitor and chemotherapy is equivalent and may indeed be inferior to chemotherapy alone, even if EGFR is functional and its phosphorylation effectively inhibited. Our data show that the interaction of EGFR-TKIs and chemotherapy is complex and suggest that other growth factors may activate the downstream signaling events. 相似文献
53.
Baruch Modan Angela Chetrit Esther Alfandary Arnon Tamir Ayala Lusky Michael Wolf Ofer Shpilberg 《The Laryngoscope》1998,108(7):1095-1097
Objective: To assess the risk of neoplastic development among persons exposed to scalp irradiation. Study Design: Historical cohort study initially; prospective follow-up subsequently. Method: Two control groups—population and siblings—matched for age, sex, ethnic origin, and year of immigration. Follow-up from time of irradiation (1950s) until the end of 1991. Linkage with nationwide cancer registry. Results: A 4.5–fold incidence of cancer (P < .01) and a 2.6–fold increase of benign tumors were noted. The mean length of latency period until tumor development was 11 years for malignant tumors and 21.5 years for benign. A clear dose response effect for both cancer and benign tumors was demonstrated. Conclusions: The study confirms the role of radiation in salivary gland carcinogenesis. It indicates a need for better awareness, a comprehensive examination, and long-term follow-up of patients who have been subjected to head and neck radiation. 相似文献
54.
Amir Shmueli Mario Baras Charles L. Sprung 《Health services & outcomes research methodology》2004,5(3-4):163-174
Intensive Care Units (ICU) are one of the most powerful and expensive technologies within inpatient care. However, its effect
on survival is still an issue under discussion. The objective of this paper is to assess the effect of General ICU on in-hospital
survival. We assessed the effect of ICU on survival using Linear and Probit regressions. Since admission to IC is not random
and depends on unobserved (to the researcher) heterogeneity, we reassessed the IC effect by Instrumental Variables (IV) and
Bivariate Probit techniques, using crowding in the IC unit as an instrument. The results show that a simple Probit of the
IC effect on survival is 7–10 percentage-points (pts). The IV estimate of the IC effect on survival is 21–34 pts, and the
Bivariate Probit estimate is 17–21 pts.
We conclude that although admitted patients are at lower risk of death, as determined by their observable (to the researcher)
characteristics, controlling for observable differences, those with a higher unobserved risk of mortality are more likely
to be admitted. The implications for an optimal admission policy are discussed. 相似文献
55.
56.
Potentiation of tumor response to radiation or chemoradiation by selective cyclooxygenase-2 enzyme inhibitors 总被引:15,自引:0,他引:15
Nakata E Mason KA Hunter N Husain A Raju U Liao Z Ang KK Milas L 《International journal of radiation oncology, biology, physics》2004,58(2):369-375
Cyclooxygenase-2 (COX-2) is an enzyme expressed primarily in pathologic states, such as inflammatory disorders and cancer, where it mediates prostaglandin production. Its overexpression is associated with more aggressive biologic tumor behavior and adverse patient outcome. Increasing evidence shows that agents that selectively inhibit COX-2 enhance tumor response to radiation or chemotherapeutic agents. This article gives an overview of some of this evidence. In addition, we describe new results showing that celecoxib, a selective COX-2 inhibitor, enhanced response of A431 human tumor xenografts in nude mice to radiation by an enhancement factor (EF) of 1.43 and to the chemotherapeutic agent docetaxel by an EF of 2.07. Celecoxib also enhanced tumor response when added to the combined docetaxel plus radiation treatment (EF = 2.13). Further experiments showed that selective COX-2 inhibitors enhanced tumor cell sensitivity to ionizing radiation, involving inhibition of cellular repair from radiation damage and cell cycle redistribution as mechanisms for some cell types. The results show that selective COX-2 inhibitors have the potential to improve tumor radiotherapy or radiochemotherapy, and this therapeutic strategy is currently under clinical testing. 相似文献
57.
58.
El-Shawarby SA Ravhon A Skull J Ellenbogen A Trew G Lavery S 《Reproductive biomedicine online》2008,17(4):549-552
The aim of this study was to compare the efficacy of two embryo transfer catheters: Wallace and Rocket Embryon in an IVF programme of a tertiary referral university centre. A total of 308 patients undergoing embryo transfer were prospectively randomized to either a transfer with the Wallace catheter or a transfer with the Rocket catheter. The main outcome measure in this study was the clinical pregnancy rate, and secondary outcome measures included implantation rate, visibility of the catheter under ultrasound, number of retained embryos post transfer, and whether change of catheter was required. In addition, patient discomfort during the procedure was recorded. Pregnancy and implantation rates were similar when Wallace or Rocket catheters were used. However, for the Rocket catheter, the tip was more often clearly seen on ultrasound and it had a lower rate of retained embryos in the catheter after transfer (P < 0.05). Experience with different transfer catheters is recommended for difficult cases. 相似文献
59.
60.
Moayad Khatib Gabby Elbaz-Greener Orna Nitzan Soboh Soboh Avi Peretz Evgeni Hazanov Wadia Kinany Yusra Halahla Liza Grosman-Rimon Helene Houle Offer Amir Shemy Carasso 《Journal of digital imaging》2022,35(6):1654
Lower respiratory infection was reported as the most common fatal infectious disease. Community-acquired pneumonia (CAP) and myocardial injury are associated; yet, true prevalence of myocardial injury is probably underestimated. We assessed the rate and severity of myocardial dysfunction in patients with CAP. Admitted patients diagnosed with CAP were prospectively recruited. All the patients had C-reactive protein (CRP), brain natriuretic peptide (BNP), and high-sensitivity cardiac troponin (hs-cTnl) tests added to their routine workup. 2D/3D Doppler echocardiography was done on a Siemens Acuson SC2000 machine ≤ 24 h of diagnosis. 3D datasets were blindly analyzed for 4-chamber volumes/strains using EchobuildR 3D-Volume Analysis prototype software, v3.0 2019, Siemens-Medical Solutions. Volume/strain parameters were correlated with admission clinical and laboratory findings. The cohort included 34 patients, median age 60 years (95% CI 55–72). The cohort included 18 (53%) patients had hypertension, 9 (25%) had diabetes mellitus, 7 (21%) were smokers, 7 (21%) had previous myocardial infarction, 4 (12%) had chronic renal failure, and 1 (3%) was on hemodialysis treatment. 2D/Doppler echocardiography findings showed normal ventricular size/function (LVEF 63 ± 9%), mild LV hypertrophy (104 ± 36 g/m2), and LA enlargement (41 ± 6 mm). 3D volumes/strains suggested bi-atrial and right ventricular dysfunction (global longitudinal strain RVGLS = − 8 ± 4%). Left ventricular strain was normal (LVGLS = − 18 ± 5%) and correlated with BNP (r = 0.40, p = 0.024). The patients with LVGLS > − 17% had higher admission blood pressure and lower SaO2 (144 ± 33 vs. 121 ± 20, systolic, mmHg, p = 0.02, and 89 ± 4 vs. 94 ± 4%, p = 0.006, respectively). hs-cTnl and CRP were not different. Using novel 3D volume/strain software in CAP patients, we demonstrated diffuse global myocardial dysfunction involving several chambers. The patients with worse LV GLS had lower SaO2 and higher blood pressure at presentation. LV GLS correlated with maximal BNP level and did not correlate with inflammation or myocardial damage markers. 相似文献