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排序方式: 共有9094条查询结果,搜索用时 31 毫秒
1.
Hiroki Koshimichi Yoshiyuki Tsuda Toru Ishibashi Toshihiro Wajima 《Journal of pharmaceutical sciences》2019,108(5):1896-1904
Baloxavir marboxil, a prodrug that is metabolized to baloxavir acid, suppresses viral replication by inhibiting cap-dependent endonuclease. Our aim is to characterize its pharmacokinetics and exposure-response relationships. Population pharmacokinetic analysis of the baloxavir acid was performed using 8310 plasma concentration data points from 1109 subjects. Exposure-response analyses were performed regarding the time to alleviation of symptoms and the reduction in the influenza virus titer. A 2-compartment model with first-order absorption and lag time well described the plasma concentration data for baloxavir acid, and body weight and race were found to be the most important factors influencing the clearance and distribution volume. A dose regimen based on the body weight (40 mg for patients weighing <80 kg and 80 mg for patients weighing ≥80 kg) could provide sufficient exposures for expecting efficacy irrespective of body weight or race; however, the exposures were dependent on the body weight and race. Exposure-response analyses suggested that the reduction in the influenza virus titer was greater in any exposure-based groups in baloxavir marboxil treatment than in the oseltamivir phosphate treatment and placebo groups. In conclusion, the population pharmacokinetic model and exposure-response relationships would be useful for understanding the pharmacokinetic and pharmacodynamic characteristics of baloxavir acid. 相似文献
2.
Jun Agata Nobuyuki Ura Hideaki Yoshida Yasuyuki Shinshi Haruki Sasaki Masaya Hyakkoku Shinya Taniguchi Kazuaki Shimamoto 《Hypertension research》2006,29(11):865-874
Angiotensin II receptor blockers (ARBs) are widely used for the treatment of hypertension. It is believed that treatment with an ARB increases the level of plasma angiotensin II (Ang II) because of a lack of negative feedback on renin activity. However, Ichikawa (Hypertens Res 2001; 24: 641-646) reported that long-term treatment of hypertensive patients with olmesartan resulted in a reduction in plasma Ang II level, though the mechanism was not determined. It has been reported that angiotensin 1-7 (Ang-(1-7)) potentiates the effect of bradykinin and acts as an angiotensin-converting enzyme (ACE) inhibitor. It is known that ACE2, which was discovered as a novel ACE-related carboxypeptidase in 2000, hydrolyzes Ang I to Ang-(1-9) and also Ang II to Ang-(1-7). It has recently been reported that olmesartan increases plasma Ang-(1-7) through an increase in ACE2 expression in rats with myocardial infarction. We hypothesized that over-expression of ACE2 may be related to a reduction in Ang II level and the cardioprotective effect of olmesartan. Administration of 0.5 mg/kg/day of olmesartan for 4 weeks to 12-week-old stroke-prone spontaneously hypertensive rats (SHRSP) significantly reduced blood pressure and left ventricular weight compared to those in SHRSP given a vehicle. Co-administration of olmesartan and (D-Ala7)-Ang-(1-7), a selective Ang-(1-7) antagonist, partially inhibited the effect of olmesartan on blood pressure and left ventricular weight. Interestingly, co-administration of (D-Ala7)-Ang-(1-7) with olmesartan significantly increased the plasma Ang II level (453.2+/-113.8 pg/ml) compared to olmesartan alone (144.9+/-27.0 pg/ml, p<0.05). Moreover, olmesartan significantly increased the cardiac ACE2 expression level compared to that in Wistar Kyoto rats and SHRSP treated with a vehicle. Olmesartan significantly improved cardiovascular remodeling and cardiac nitrite/ nitrate content, but co-administration of olmesartan and (D-Ala7)-Ang-(1-7) partially reversed this anti-remodeling effect and the increase in nitrite/nitrate. These findings suggest that olmesartan may exhibit an ACE inhibitory action in addition to an Ang II receptor blocking action, prevent an increase in Ang II level, and protect cardiovascular remodeling through an increase in cardiac nitric oxide production and endogenous Ang-(1-7) via over-expression of ACE2. 相似文献
3.
Akira Sawaki Nobumasa Mizuno Kuniyuki Takahashi Tsuneya Nakamura Masahiro Tajika Hiroki Kawai Toshifumi Isaka Hiroshi Imaoka Yasuyuki Okamoto Masatoshi Aoki Hiroyuki Inoue Ahmed AS Salem Yasushi Yatabe Kenji Yamao 《Digestive endoscopy》2006,18(1):40-44
Background: Gastrointestinal stromal tumors (GIST) are one of the most common mesenchymal tumors of the gastrointestinal tract. GIST are defined by positive immunohistochemical staining for KIT or CD34 and thus are generally diagnosed after surgery. Because small GIST are rarely diagnosed before surgery, the clinical course of these small tumors is not clear. The aim of the present study was to follow changes in size and configuration of small GIST that were pathologically confirmed using endoscopic ultrasonography‐guided fine‐needle aspiration biopsy (EUS‐FNAB). Methods: Between July 1997 and December 2003, 16 tumors in 16 patients (10 men and 6 women) with an immunohistochemical diagnosis of GIST were regularly followed in our hospital. The median patient age when EUS‐FNAB was performed was 62 years (range 26–82 years) and the median follow‐up period was 4.9 years (range 0.5–9.6 years). Results: Fourteen tumors showed no remarkable changes in size and shape during follow up compared with the initial diagnosis. Two tumors enlarged: one tumor approximately doubled its diameter in 8 years and the other tumor increased from 1.8 cm at diagnosis to up to 10 cm after only 2 years. Doubling time of the latter tumor was calculated as 3.1 months. Conclusions: We conclude that EUS‐FNAB might be a good modality for final diagnosis of GIST without surgery, and that GIST without rapid growth on follow up can be endoscopically followed. 相似文献
4.
Yasuyuki Suzuki Kazuyuki Daitoku Masahito Minakawa Kozo Fukui Ikuo Fukuda 《The Japanese Journal of Thoracic and Cardiovascular Surgery》2006,54(1):44-46
We report the case of a 4-year-old girl who had quadricuspid aortic valve regurgitation with tetralogy of Fallot and pulmonary
atresia. This combination is very uncommon. Aortic valve replacement was performed successfully due to aortic regurgitation
which had progressed one year after the total repair. The dilated aortic annulus plus quadricuspid aortic valve may result
in progressive aortic regurgitation for a short period. 相似文献
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Y Abiko K Ichihara K Sakai H Sashida T Ishibashi 《Methods and findings in experimental and clinical pharmacology》1986,8(5):271-278
This paper describes a method by which antianginal drugs can be evaluated in the dog heart in situ. Myocardial pH was measured continuously by a micro glass pH electrode inserted in the left ventricular endocardial layers of the dog anesthetized with pentobarbital. Occlusion of the left anterior descending coronary artery (LAD) decreased myocardial pH, and release of the LAD restored the pH. The myocardial acidosis induced by ischemia was metabolic in nature and accompanied by a decrease in the levels of adenosine triphosphate and creatine phosphate and an increase in the levels of lactate in the myocardium. Drugs were injected intravenously 30 min after incomplete (partial) occlusion ot the LAD, lasting until 60 min after drug injection. Propranolol, atenolol, and sotalol markedly attenuated the myocardial pH that had been decreased by LAD occlusion. Nitroglycerin, diltiazem, and nicorandil also attenuated the pH, but these drugs were less active in attenuating myocardial acidosis. Dipyridamole, nifedipine, and beta-2 adrenoceptor antagonists were least active in this regard. It is concluded that myocardial pH can be used as an indicator of myocardial regional ischemia and utilized for evaluation of antianginal drugs. 相似文献
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