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71.
The lower limits of the "therapeutic range" for serum levels of sodium valproate (VPA) were evaluated in epileptic children showing a benign clinical course. Twenty-five outpatients, aged 5 to 16 years, whose seizures were well controlled over three years with VPA alone, were studied. Venous blood was taken 1.1 to 5 hrs after the morning dose. Serum VPA concentrations at steady-state after receiving the maintenance doses to control seizures were determined by enzyme immunoassay. The patients were divided into three groups according to the seizure type and the age at onset; A and B: patients with tonic and/or clonic seizures, aged below 3 yrs (n = 11) and 3 to 11 yrs (n = 6), respectively, C: those with absence seizures, aged 4 to 11 yrs (n = 8). The serum concentrations in A (47.8 +/- 21.6 micrograms/ml, mean +/- SD) were significantly (p less than 0.02) lower than those in groups B and C (85.2 +/- 14.0 and 73.0 +/- 17.4 micrograms/ml, respectively). VPA concentrations below 50 micrograms/ml were seen in 6 patients (55%) in group A. It was concluded that many epileptic children, whose ages at onset were below 3 yrs, with tonic and/or clonic seizures could be controlled even with low initial serum concentrations below the "therapeutic range". 相似文献
72.
Takuma Narita Shingo Hatakeyama Shintaro Narita Masahiro Takahashi Toshihiko Sakurai Sadafumi Kawamura Senji Hoshi Jiro Shimoda Toshiaki Kawaguchi Shigeto Ishidoya Koji Mitsuzuka Yoichi Arai Akihiro Ito Norihiko Tsuchiya Tomonori Habuchi Chikara Ohyama 《Translational andrology and urology》2021,10(1):417
BackgroundThe clinical benefit of the combined androgen blockade (CAB) therapy over luteinizing hormone-releasing hormone analog (LH-RHa) monotherapy for hormone naïve metastatic prostate cancer (mHNPC) is unclear. Therefore, we retrospectively compare the effectiveness of CAB with the LH-RHa monotherapy on the prognosis of Japanese patients with mHNPC.MethodsWe retrospectively evaluated the prognosis of 517 patients diagnosed with mHNPC between August 2001 and May 2017. The patients’ data were obtained from the Michinoku Urological Cancer Research Group database and Hirosaki University-related hospitals. Patients were divided into the CAB and LH-RHa monotherapy groups based on primary androgen deprivation therapy (ADT). Overall survival (OS), cancer-specific survival (CSS), and castrate-resistant prostate cancer-free survival (CRPC-FS) were compared between the two groups using the Kaplan-Meier curve analysis. Inverse probability of treatment weighting (IPTW)-adjusted Cox hazard proportional analyses was performed to investigate the effect of primary ADT on oncological outcomes.ResultsThe median age was 73 years old. The numbers of patients in the CAB and LH-RHa monotherapy groups were 447 and 70, respectively. The Kaplan-Meier curve analysis showed no significant differences in either 5-year OS (56.7% vs. 52.5%, P=0.277), CSS (61.1% vs. 56.4%, P=0.400), and CRPC-FS (33.1% vs. 31.1%, P=0.529) between the groups. IPTW-adjusted multivariate Cox hazard proportional analyses showed no significant differences in OS, CSS, and CRPC-FS between the two groups.ConclusionsNo significant differences in oncological outcomes were observed between the CAB and LH-RHa monotherapy groups in patients with mHNPC. 相似文献
73.
Jun Yoshida Masaaki Mizuno Itaru Inoue Toshihiko Wakabayasi Kenichiro Sugita Hisao Seo Kazumi Chiba 《Journal of neuro-oncology》1990,8(3):221-229
Summary Monoclonal antibody (MCA) G-22 is directed against a human glioma-associated surface antigen. Its availability for the radioimmunodetection of human glioma was analyzed by utilizing the xenografts in athymic mice. Nude mice with subcutaneous grafts of U251-MG or U251-SP glioma received intravenous administration of 123I or 131I labeled F(ab)2 fragment or whole immunoglobulin. Results of radioimaging revealed that 123I-labeled antibody was better than the 131I-labeled. It was also noted that administration of 123I-labeled F(ab)2 fragment of G-22 MCA enabled the imaging of human glioma xenografts weighing 80–650 mg after 48 hours. When biodistribution of 123I MCA was compared between G-22 and control antibodies, the percentages of dose/g in tumors were 5.228–1.799 at 30 hours and 4.112–1.132 at 48 hours with G-22 and they were 4.164–1.248 and 0.314–0.142 with control. The tumor/blood ratio until 72 hours after injection was constantly above 1 with G-22 and less than 1 with control antibody. These results indicate the potential usefulness of G-22 MCA for the radioimmunodetection of human gliomas. 相似文献
74.
Tomoaki Yuhi Akihiko Wada Ryuichi Yamamoto Masanobu Urabe Hiromi Niina Futoshi Izumi Toshihiko Yanagital 《Naunyn-Schmiedeberg's archives of pharmacology》1994,350(2):209-212
We have previously reported that in bovine adrenal chromaffin cells Ptychodiscus brevis toxin-3 (PbTx-3) does not alter the veratridine-induced 22Na influx when given alone, but increases the influx of 22Na when co-applied with either - or -scorpion venom (Wada et al. 1992). In the present study, we characterized [3H]PbTx-3 binding in bovine adrenal chromaffin cells. [3H]PbTx-3 binding was saturable, reversible and of high-affinity with an equilibrium dissociation constant (Kd) of 32.0±4.9 nmol/1 and a maximum binding capacity Bmax of 6.2 ± 1.2 pmol/4 × 106 cells (4.5 ± 0.9 pmol/mg cell protein). A Hill plot revealed the lack of cooperative interaction among the binding sites. Unlabelled PbTx-3 inhibited [3H]PbTx-3 binding with an IC50 of 31 nmol/l. However, tetrodotoxin, veratridine, - and -scorpion venom, or veratridine in combination with either - or -scorpion venom did not alter [3H]PbTx-3 binding. All these results suggest that PbTx-3 binds to a site (site 5) distinct from the previously known four toxin binding sites, which does not gate voltage-dependent Na channels by itself, but is specifically involved in the allosteric modulation of Na channels in adrenal medullary cells.
Correspondence to: A. Wada at the above address 相似文献
75.
76.
Most immunosuppresive drugs are absorbed from the intestine after oral administration, although there is some difference of bioavailability between ileum and jejunum. Using an orthotopic segmental small bowel transplantation (SBT) model in rats, we studied the pharmacokinetic profiles of cyclosporin A and tacrolimus concentrations after oral intake, comparing jejunal and ileal transplanted rats. Two types of segmental SBT (jejunal and ileal SBT) in a syngeneic combination were performed. After oral administration of cyclosporin A (10mgkg(-1) or tacrolimus (5 mg kg(-1)), pharmacokinetic data were obtained from the long-surviving rats transplanted with segmental SBT. To determine the effect of additional bile on cyclosporin absorption, an emulsion of cyclosporin A with fresh bile juice was re-challenged on segmental SBT rats before killing. A histological study was also performed by use of the intestinal grafts from the killed SBT rats. A higher concentration of cyclosporin A was observed in the ileum-grafted rats than in the rats which received the jejunal grafts. Oral bioavailability of cyclosporin A in ileal SBT rats tended to be increased by addition of fresh bile juice, but that in jejunal SBT rats did not change. On the other hand, there was no significant difference of tacrolimus concentration between jejunum- and ileum-transplanted rats. Histological studies showed that the superficial mucosal layer of both grafts, but especially the ileal graft, was markedly elongated compared with that of normal intestine. The present study showed that cyclosporin A was more actively absorbed from ileum than from jejunum in SBT, but tacrolimus was absorbed equally from both sites. These data suggest that cyclosporin A concentration is satisfactorily controlled in the segmental ileal graft, while there is no difference of tacrolimus absorption between ileal and jejunal graft. 相似文献
77.
The ultrastructure of parapapillary chorioretinal atrophy in eyes with secondary angle closure glaucoma 总被引:4,自引:0,他引:4
Toshiaki Kubota Ursula M. Schlötzer-Schrehardt Gottfried O. H. Naumann Toshihiko Kohno Hajime Inomata 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》1996,234(6):351-358
Background: The present study was performed to investigate the ultrastructure of deep retinal layers and choroid corresponding to the parapapillary chorioretinal atrophy in eyes with secondary angle-closure glaucoma. Methods: The glaucomatous eyes included two eyes enucleated due to iris ring melanoma with high intraocular pressure and one eye with neovascular glaucoma enucleated due to ocular pain. The control eyes included one eye enucleated due to choroidal malignant melanoma with normal intraocular pressure and one eye enucleated during surgery for supramandibular carcinoma. These eyes were studied with light and electron microscopy. Results: In the region of parapapillary chorioretinal atrophy of glaucomatous eyes, the retinal pigment epithelial cells showed degenerative changes, such as loss of basal in foldings and microvilli, degenerated mitochondria, vacuolar degeneration and irregular distribution of melanin granules. The photoreceptors were decreased in number in this area of glaucomatous eyes. The lumen of the choriocapillary vessels adjacent to the optic nerve was collapsed. Conclusion: These results elucidate the fine structures of deep retina and choroid in the region of parapapillary chorioretinal atrophy of glaucomatous eyes, and suggest that the reduced choroidal perfusion might be the pathogenetic mechanism of glaucomatous parapapillary chorioretinal atrophy. 相似文献
78.
Kazuaki Yamaoka MD Toshihiko Nouchi MD Fumiaki Marumo MD Dr. Chifumi Sato MD 《Digestive diseases and sciences》1993,38(8):1473-1479
To determine the significance of the expression of -smooth-muscle actin in the fibrotic human liver, normal and diseased livers were stained with anti--smooth-muscle-actin antibody by an immunoperoxidase method. Vitamin A-containing lipocytes were also identified by the modified Kupffer's gold chloride method. In the normal human liver, lipocytes as well as vascular smooth muscle cells expressed -smooth-muscle actin. In alcoholic liver disease, there was an increase in the cells positive for -smooth-muscle actin adjacent to the fibrotic areas, but the response of lipocytes to the gold chloride reaction diminished. In chronic hepatitis, the cells positive for -smooth-muscle actin increased around the enlarged portal areas, and the response to the gold chloride reaction did not change appreciably. An increase in the cells positive for -smooth-muscle actin was associated with the progression of hepatic fibrosis in the liver of patients with alcoholic liver disease and chronic hepatitis. 相似文献
79.
Tohru Ozaki Toshihiko Uematsu Satoru Nagashima Masahiko Nishimoto Mitsuyoshi Nakashima 《Naunyn-Schmiedeberg's archives of pharmacology》1991,344(4):478-487
Summary DPI 201-106 (DPI), a novel and potent cardiotonic agent, exhibits its effects by prolonging the open state of Na+ channels, resulting in an increase in action potential duration, and thus, is supposed to share the class III antiarrhythmic activity. The effects of DPI on the hemodynamics, intraventricular conduction and refractoriness of heart, and the incidence of arrhythmias induced by programmed electrical ventricular stimulation (PES) were compared with (±)-dobutamine. Dogs which survived for 5 to 7 days after the induction of myocardial infarction were used as the model. The presence of sub-acute myocardial infarction caused by occluding the left anterior descending coronary artery elicited a mild left ventricular dysfunction represented by a significant decrease in peak LV dp/dt by about 20%.Both i.v. bolus injection of DPI (1, 3 and 5 mg/kg) and i. v. continuous infusion of dobutamine (3, 5 and 10 g/kg/min), which were administered in a cumulative manner, dose-dependently improved the hemodynamic parameters. At the higher doses of both DPI (3 and 5 mg/kg) and dobutamine (5 and 10 g/kg/min) the control values were reached or even exceeded. DPI dose-dependently increased the effective refractory period (ERP) of both non-infarcted and infarcted ventricular myocardia to a similar degree, but the conduction time showed a frequency-dependent increase in the infarcted myocardium to a greater degree than in the non-infarcted myocardium after DPI. In contrast, dobutamine decreased the ERP in both non-infarcted and infarcted myocardia, and slightly increased the difference of refractoriness between the non-infarcted and infarcted zones with no effect on the intraventricular conduction. In the PES study, DPI (3 and 5 mg/kg) produced a significant decrease in the incidence of ventricular tachycardia, whereas dobutamine (5 and 10 g/kg/min) tended to worsen the arrhythmias. These findings suggest that cardiotonic agents with a class III antiarrhythmic property such as DPI may be potentially useful for the management of heart failure accompanied by ischemic heart disease.Abbreviations DPI, DPI 201-106; PES
programmed electrical ventricular stimulation
- LV dp/dt
the rate of rise of left ventricular pressure
- ERP
effective refractory period
- RVOT
right ventricular outflow tract
- VT
ventricular tachycardia
- LAD
left anterior discending coronary artery
Send offprint requests to T. Uematsu at the above address 相似文献
80.
Toshihiko Kotake Tsuneharu Miki Hideyuki Akaza Yoshinobu Kubota Yasunori Nishio Yosuke Matsumura Kazuo Ota Nobuya Ogawa 《Cancer chemotherapy and pharmacology》1991,27(4):253-257
Summary The effects of recombinant granulocyte colony-stimulating factor (rG-CSF) on the myelosuppression, especially neutropenia, induced by cancer chemotherapy in patients with urogenital cancer were investigated in a randomized, controlled clinical study. In this study, rG-CSF was given subcutaneously at a dose of 2 g/kg per day for 14 consecutive days. Changes in neutrophil counts were compared between the first (no rG-CSF) and second cycles (rG-CSF treatment period) of chemotherapy. rG-CSF administration was found to be effective in reducing the duration of neutropenia, in elevating the neutrophil nadir, and in reducing recovery time. Based on comparisons between the randomized rG-CSF treatment group (with rG-CSF) and the control group, treatment with rG-CSF resulted in the moderation or prevention of neutropenia and the acceleration of recovery. These results demonstrate that in chemotherapy of patients with urogenital cancer, in which neutropenia is a dose- or schedule-limiting factor, the concomitant use of rG-CSF may enable an increase in the dose (higher single dose or increased dose per unit of time) or shorten the chemotherapy period. 相似文献