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991.
992.
993.
Cheng L Roth LM Zhang S Wang M Morton MJ Zheng W Abdul Karim FW Montironi R Lopez-Beltran A 《Cancer》2011,117(10):2096-2103
BACKGROUND:
Dysgerminoma, the ovarian counterpart of seminoma, is the most common type of malignant ovarian germ cell tumor. The role of KIT mutation and amplification in the development of dysgerminoma is not currently established. The purpose of this study was to analyze alterations of the KIT gene in a large series of dysgerminomas and correlate the findings with clinicopathological parameters.METHODS:
Dysgerminoma cells from 22 patients were analyzed for KIT mutations at exon 17 codon 816. KIT amplification and chromosome 12p anomalies were investigated by way of dual color fluorescence in situ hybridization. KIT protein expression was also examined by way of immunohistochemistry.RESULTS:
KIT exon 17 codon 816 mutations and KIT amplification were each detected in 6 cases of dysgerminoma (27%); however, there was no correlation between these 2 factors. KIT expression was detected in 87% of dysgerminomas. The KIT mutation was associated with advanced pathological stage (P < .05), and KIT amplification was associated with elevated KIT protein expression (P < .05). Chromosome 12p anomalies were found in 82% of the dysgerminomas and did not correlate with KIT abnormalities.CONCLUSIONS:
KIT mutations occur in approximately one‐third of cases of dysgerminomas and are associated with advanced stage at presentation. KIT is a potential therapeutic target for those dysgerminomas that have the mutation. Cancer 2011. © 2010 American Cancer Society. 相似文献994.
Chamie K Kurzrock EA Evans CP Litwin MS Koppie TM Wootton-Gorges SL Boone JM Lara PN Devere White RW 《Cancer》2011,117(18):4219-4230
BACKGROUND:
Men on active surveillance for clinical stage I nonseminomatous germ cell tumor (NSGCT) undergo frequent computed tomography imaging to avoid delayed detection of disease. Irradiation from frequent imaging and chemotherapy upon progression may place patients at increased risk of a second malignancy. In this study, the authors sought to identify such an increased risk among men who chose initial surveillance for NSGCT.METHODS:
The authors utilized data from the Surveillance, Epidemiology and End Results Program and stratified the cohort based on whether they underwent retroperitoneal lymph node dissection (RPLND). A propensity‐score model was used to adjust for covariates, and a competing‐risks regression analysis was performed to estimate cumulative incidence rates of second malignancy. Incidence risk ratios were predicted by using the cumulative incidence rates per 10,000 patients.RESULTS:
There was no statistically significant increase in the incidence of a secondary malignancy for the entire cohort of testicular cancer survivors. However, when the analysis was restricted to patients with clinical stage I NSGCT, nonsurgical management only in those aged >45 years was an independent predictor of developing a second malignancy. For every 10,000 patients with stage I NSGCT who chose to forego RPLND, an absolute excess incidence of 22, 52, and 73 secondary malignancies would be diagnosed at 5 years, 10 years, and 15 years, respectively.CONCLUSIONS:
The current results indicated that patients aged >45 years who forego RPLND for T1 or T2 clinical stage I NSGCT are more likely to develop a second malignancy than those who do undergo RPLND. Nonsurgical management of NSGCT may be associated with more long‐term health risks than primary RPLND. Cancer 2011;. © 2011 American Cancer Society. 相似文献995.
Negretti L Bouchireb K Levy-Piedbois C Habrand JL Dhermain F Kalifa C Grill J Dufour C 《Journal of neuro-oncology》2011,104(3):773-777
We report herein our institutional experience in the treatment of diffuse intrinsic pontine glioma (DIPG) with a hypofractionated
external-beam radiotherapy schedule. Between April 1996 and January 2004, 22 patients (age 2.9–12.5 years) with newly diagnosed
DIPG were treated by hypofractionated radiation therapy delivering a total dose of 45 Gy in daily fractions of 3 Gy, given
over 3 weeks. No other treatment was applied concomitantly. Fourteen of the 22 patients received the prescribed dose of 45 Gy
in 15 fractions of 3 Gy, and 2 patients received a total dose of 60 and 45 Gy with a combination of two different beams (photons
and neutrons). In five cases the daily fraction was modified to 2 Gy due to intolerance, and one patient died due to serious
intracranial hypertension after two fractions of 3 Gy and one of 2 Gy. Among 22 children, 14 patients showed clinical improvement,
usually starting in the second week of treatment. No grade 3 or 4 acute toxicity from radiotherapy was observed. No treatment
interruption was needed. In six patients, steroids could be discontinued within 1 month after the end of radiotherapy. Median
time to progression and median overall survival were 5.7 months and 7.6 months, respectively. External radiotherapy with a
radical hypofractionated regimen is feasible and well tolerated in children with newly diagnosed DIPG. However, this regimen
does not seem to change overall survival in this setting. It could represent a short-duration alternative to more protracted
regimens. 相似文献
996.
David B Bonnefont-Rousselot D Oudina K Degat MC Deschepper M Viateau V Bensidhoum M Oddou C Petite H 《Tissue engineering. Part C, Methods》2011,17(5):505-516
A perfusion bioreactor, which was designed based on fluidized bed concepts, was validated for the culture of bone constructs of clinically relevant size. For this study, natural coral has been used as three-dimensional scaffolds. This biomaterial is a microporous, biocompatible, osteoconductive, and absorbable scaffold. This perfusion bioreactor provided a stable environment in terms of osmolarity, pH, and, most importantly, oxidative stress. Bone constructs engineered in this system resulted in significantly higher cell proliferation and homogenous cell distribution than those cultured under static conditions. Particularly relevant to the production of bioengineered bone in a clinical setting, custom-made bone constructs (each one with volume up to 30 cm(3)) could be produced using a such perfusion bioreactor. Last, but not least, the bone constructs of clinically relevant volume thus produced were shown to be osteogenic when transplanted subcutaneously in sheep. 相似文献
997.
Fernandez SP Karim N Mewett KN Chebib M Johnston GA Hanrahan JR 《British journal of pharmacology》2012,165(4):965-977
BACKGROUND AND PURPOSE
Enhancement of GABAergic function is the primary mechanism of important therapeutic agents such as benzodiazepines, barbiturates, neurosteroids, general anaesthetics and some anticonvulsants. Despite their chemical diversity, many studies have postulated that these agents may bind at a common or overlapping binding site, or share an activation domain. Similarly, we found that flavan-3-ol esters act as positive modulators of GABAA receptors, and noted that this action resembled the in vitro profile of general anaesthetics. In this study we further investigated the interactions between these agents.EXPERIMENTAL APPROACH
Using two-electrode voltage clamp electrophysiological recordings on receptors of known subunit composition expressed in Xenopus oocytes, we evaluated positive modulation by etomidate, loreclezole, diazepam, thiopentone, 5α-pregnan-3α-ol-20-one (THP) and the flavan-3-ol ester 2S,3R-trans 3-acetoxy-4′-methoxyflavan (Fa131) on wild-type and mutated GABAA receptors.KEY RESULTS
The newly identified flavan, 2S,3S-cis 3-acetoxy-3′,4′-dimethoxyflavan (Fa173), antagonized the potentiating actions of Fa131, etomidate and loreclezole at α1β2 and α1β2γ2L GABAA receptors. Furthermore, Fa173 blocked the potentiation of GABA responses by high, but not low, concentrations of diazepam, but did not block the potentiation induced by propofol, the neurosteroid THP or the barbiturate thiopental. Mutational studies on ‘anaesthetic-influencing’ residues showed that, compared with wild-type GABAA receptors, α1M236Wβ2γ2L and α1β2N265Sγ2L receptors are resistant to potentiation by etomidate, loreclezole and Fa131.CONCLUSIONS AND IMPLICATIONS
Fa173 is a selective antagonist that can be used for allosteric modulation of GABAA receptors. Flavan-3-ol derivatives are potential ligands for etomidate/loreclezole-related binding sites at GABAA receptors and the low-affinity effects of diazepam are mediated via the same site. 相似文献998.
Gengiah TN Holford NH Botha JH Gray AL Naidoo K Abdool Karim SS 《European journal of clinical pharmacology》2012,68(5):689-695
Purpose
Drug interactions are of concern when treating patients co-infected with human immunodeficiency virus (HIV) and tuberculosis. Concomitant use of efavirenz (EFV) with the enzyme inducer rifampicin might be expected to increase EFV clearance. We investigated the influence of concomitant tuberculosis treatment on the plasma clearance of EFV. 相似文献999.
1000.
Annane D Chadda K Gajdos P Jars-Guincestre MC Chevret S Raphael JC 《Intensive care medicine》2011,37(3):486-492