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91.
Carlo Barone Michele Basso Giovanni Schinzari Carmelo Pozzo Nunziatina Trigila Ettore D'Argento Michela Quirino Antonio Astone Alessandra Cassano 《Gastric cancer》2007,10(2):104-111
Background In advanced gastric cancer few data are available on the efficacy or safety of new drug combination regimens after progression
following first-line chemotherapy.
Methods Patients with histologically confirmed advanced gastric cancer and Eastern Cooperative Oncology Group (ECOG) performance status
(PS) less than 2, progressing after first-line chemotherapy, were eligible. Patients were treated with docetaxel 75 mg/m2 on day 1 and oxaliplatin 80 mg/m2 on day 2, every 3 weeks, until progression or unacceptable toxicity.
Results Between May 2002 and April 2005, 38 patients were enrolled. Men accounted for 73.7% of the patients and the median age was
59 years. The primary tumor was not resected in 47.4% of the patients; the peritoneum was the most frequent metastatic site
(60.5%). The first-line treatment was cisplatin, epirubicin, and infusional 5-fluorouracil (ECF) in 81.5% of the patients
and cisplatin and infusional 5-fluorouracil (CF) in 15.7%. The median number of cycles was 4.3. The treatment was well tolerated,
with no toxic deaths. National Cancer Institute (NCI) grade III-IV neutropenia was frequent (26.3%), but no febrile neutropenia
was reported. Severe asthenia (15.7%) and severe nausea (15.7%) required dose reductions in 2 patients and treatment discontinuation
in another. The overall response rate was 10.5%, and 18 patients (47.3%) experienced disease stabilization (7 of them with
significant clinical benefit). Median time to progression was 4.0 months (range, 2–8 months) and median overall survival was
8.1 months (range, 3–26 months). Thirteen patients (34.2%) also received third-line chemotherapy, with an irinotecan-containing
regimen, and their median overall survival was higher than that of the other patients (16.3 vs 6.0 months)
Conclusion The combination of oxaliplatin and docetaxel shows only marginal activity as second-line treatment, but it has a good tolerability
profile. This suggests that there is room for optimizing the schedule as well as for planning sequential treatments in gastric
cancer. 相似文献
92.
Valentina S Barbiero Roberto Giambelli Laura Musazzi Ettore Tiraboschi Daniela Tardito Jorge Perez Filippo Drago Giorgio Racagni Maurizio Popoli 《Neuropsychopharmacology》2007,32(12):2511-2519
Changes in synaptic plasticity are involved in pathophysiology of depression and in the mechanism of antidepressants. Ca(2+)/calmodulin (CaM) kinase II, a protein kinase involved in synaptic plasticity, has been previously shown to be a target of antidepressants. We previously found that antidepressants activate the kinase in hippocampal neuronal cell bodies by increasing phosphorylation at Thr(286), reduce the kinase phosphorylation in synaptic membranes, and in turn its phosphorylation-dependent interaction with syntaxin-1 and the release of glutamate from hippocampal synaptosomes. Here, we investigated the chronic effect of different antidepressants (fluoxetine, desipramine, and reboxetine) on the expression and function of the kinase in distinct subcellular compartments in order to dissect the different kinase pools affected. Acute treatments did not induce any change in the kinase. In total tissue extracts chronic drug treatments induced activation of the kinase; in hippocampus (HC), but not in prefrontal/frontal cortex, this was partially accounted for by increased Thr(286) phosphorylation, suggesting the involvement of different mechanisms of activation. In synaptosomes, all drugs reduced the kinase phosphorylation, particularly in HC where, upon fractionation of the synaptosomal particulate into synaptic vesicles and membranes, we found that the drugs induced a redistribution and differential activation of the kinase between membranes and vesicles. Furthermore, a large decrease in the level and phosphorylation of synapsin I located at synaptic membranes was consistent with the observed decrease of CaM kinase II. Overall, antidepressants induce a complex pattern of modifications in distinct subcellular compartments; at presynaptic level, these changes are in line with a dampening of glutamate release. 相似文献
93.
J Santini C Serra F Ettore O Dassonville F Demard 《Revue de stomatologie et de chirurgie maxillo-faciale》1991,92(3):179-182
Postirradiation sarcoma of the head and neck has rarely been reported. A case of malignant fibrous histiocytoma (M.F.H.) occurring in the mandible is presented. Head and neck region was previously irradiated for Hodgkin's disease. The interval from initial radiation to diagnosis of sarcoma was 10 years. Aggressive treatment with early radical excision is the treatment of choice. In spite of extensive surgery, the patient died one year after treatment with local recurrence. 相似文献
94.
Anorectal malformations and Down's syndrome 总被引:1,自引:0,他引:1
95.
96.
Franca Morazzoni Carmen Canevali Ivano Moschetti Roberto Todeschini Sergio Caroli Alessandro Alimonti Francesco Petrucci Gianni Ravasi Amedeo Vittorio Bedini Franco Milani Mauro Palazzi Sergio Villa Grabriella Giudice 《Cancer chemotherapy and pharmacology》1995,35(6):529-532
Platinum microquantities were determined in plasma of patients affected by lung carcinoma during treatment with radiotherapy (RT) and concurrent low-dose continuous infusion ofcis-dichlorodiammineplatinum(II) (CDDP). RT was given at 50 Gy in continuous course; CDDP was continuously infused at 4 mg/m2 daily for 100h/week for 5 weeks, and the infusions were separated by 68h of rest. The percentage of free drug versus total drug in plasma was about 3%. It did not vary with therapy duration and was not significantly different from that found in 5-day continuous infusions at much higher daily doses. Never-theless, maximal values of free Pt in plasma were very low and agreed with the low level of CDDP toxicity encountered on the present administration schedule. 相似文献
97.
Palatini P Malacco E Di SS Carretta R Dorigatti F Bertocchi F Mann J 《European journal of clinical pharmacology》2002,57(11):765-770
OBJECTIVE: The aim of this study was to measure the time-effect profiles of a once-daily administered valsartan/hydrochlorothiazide combination and amlodipine on blood pressure using various indices derived from 24-h ambulatory blood pressure (BP) monitoring. METHODS: Of the 310 randomized outpatients with uncomplicated mild-to-moderate primary hypertension, 259 (133 on valsartan/hydrochlorothiazide, 126 on amlodipine) were eligible for analysis. After a 2-week placebo wash-out period, the patients were randomly allocated to treatment with either valsartan 80 mg once daily (o.d.) or amlodipine 5 mg o.d. for 4 weeks; in the case of an unsatisfactory blood pressure response, the treatments could be respectively changed to the fixed combination of valsartan 80 mg plus hydrochlorothiazide 12.5 mg o.d. or amlodipine 10 mg o.d. for a further 8 weeks. The trough:peak ratio (global and individualized approaches) and smoothness index (i.e., the ratio between the average of the 24-hourly BP changes after treatment and the corresponding standard deviation) were calculated from 24-h ambulatory blood pressure recordings made after the placebo period and after 4 weeks and 12 weeks of active treatment. RESULTS: Both regimens effectively lowered systolic and diastolic ambulatory pressures after 4 weeks and 12 weeks (all P<0.001) but, among the responders, the valsartan/hydrochlorothiazide combination had a greater antihypertensive effect during the night-time hours after 12 weeks (P=0.03/0.02). In the responders, the placebo-adjusted, mean trough:peak ratios were 0.76/0.74 in the valsartan/hydrochlorothiazide group (n = 111) and 0.66/0.62 in the amlodipine group (n = 101). The corresponding global trough:peak ratios were 0.61/0.57 for the valsartan/hydrochlorothiazide combination and 0.56/0.56 for amlodipine. However, the between-group differences in individual or global trough:peak ratios were not significant. The smoothness index was slightly, but insignificantly, greater for valsartan/hydrochlorothiazide than for amlodipine in the responders and the groups as a whole. CONCLUSION: Valsartan/hydrochlorothiazide and amlodipine were equally effective in reducing ambulatory BP, but the valsartan/hydrochlorothiazide combination led to more homogeneous BP control during the inter-dosing interval. Trough:peak ratio and smoothness index did not reflect this finding accurately. 相似文献
98.
Bolognese A Correale G Manfra M Lavecchia A Mazzoni O Novellino E Barone V Pani A Tramontano E La Colla P Murgioni C Serra I Setzu G Loddo R 《Journal of medicinal chemistry》2002,45(24):5205-5216
The iminoquinone is an important moiety of a large number of antineoplastic drugs and plays a significant role in the nucleus of actinomycins, powerful, highly toxic, natural antibiotics that target DNA as intercalating agents. A series of polycyclic iminoquinonic compounds, 2-amino-3H-phenoxazin-3-one (1), 2-amino-1,9-diacetyl-3H-phenoxazin-3-one (2), 2-acetylamino-3H-phenoxazin-3-one (3), 3H-phenoxazin-3-one (4), 5H-pyrido[3,2-a]phenoxazin-5-one (5), and 5H-pyrido[3,2-a]phenothiazin-5-one (6), strictly related to the actinomycin chromophore, were synthesized for developing new anticancer intercalating drugs. The antiproliferative activity of these compounds, evaluated against representative human liquid and solid neoplastic cell lines, showed that 5 and its isoster 6 were the most active compounds inhibiting cell proliferation in a submicromolar range. Compound 5 was also evaluated against KB subclones (KBMDR, KB7D, and KBV20C), which overexpress the MDR1/P-glycoprotein drug efflux pump responsible for drug resistance. All the above KB subclones did not show altered sensitivity to the antiproliferative activity of 5. UV-vis and (1)H NMR spectroscopy experiments support the phenoxazinone 5/DNA binding. Molecular mechanics methods were used to build a three-dimensional model of the 5/[d(GAAGCTTC)]2 complex. Electrostatic interactions between the hydrogen of the positively charged pyridine nitrogen of 5 and the negatively charged oxygen atoms (O4' and O5') of the cytosine C5 residue together with stacking forces contribute to the high antiproliferative activity. The metal(II)-assisted synthesis procedure of 5 is described, and the formation mechanism is proposed. 相似文献
99.
100.
Squillaci E Fanucci E Sciuto F Masala S Sodani G Carlani M Simonetti G 《Digestive diseases and sciences》2003,48(3):449-458
The principal criterion for resectability of pancreatic carcinoma is the assessment of vascular involvement. In a prospective evaluation the ability of Spiral CT Angiography (CTA) to detect vascular involvement in 50 patients with pancreatic carcinoma, was proved; DSA was performed later in all patients. In 20 patients, without vascular involvement, a complete concordance was obtained. Of 30 patients with vascular involvement, there was complete concordance between CTA and angiography in 22 patients and discordance in 8 patients. CTA was superior in 2 cases with periadventitial infiltration and in 5 patients with splenoportal confluence thrombosis. DSA was superior in 1 case with infiltration of the superior mesenteric vein. After surgical evaluation, sensitivity of CTA and DSA was 97% and 77%, respectively, and the negative predictive values were 95% and 74%. As compared to DSA, CTA is more rapid and less invasive and can be considered the modality of choice for preoperative work-up of pancreatic neoplasm. 相似文献