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排序方式: 共有5347条查询结果,搜索用时 31 毫秒
11.
Michiko Oka Y. Itoh Shigeru Tatsumi F.-H. Ma Yojiro Ukai Yoshiaki Yoshikuni Kiyoshi Kimura 《Naunyn-Schmiedeberg's archives of pharmacology》1997,356(2):189-196
The effect of (+)-5-oxo-D-prolinepiperidinamide monohydrate (NS-105), a novel cognition enhancer, on adenylate cyclase activity
was investigated in cultured neurons of the mouse cerebral cortex. NS-105 (10–7 and 10–6 M) inhibited forskolin-stimulated cyclic AMP formation, an action that was dependent on pertussis toxin-sensitive G proteins.
Conversely, in pertussis toxin-pretreated neurons, NS-105 (10–7 –10–5 M) significantly enhanced the forskolin-stimulated cyclic AMP formation, and this action was completely reversed by cholera
toxin. A metabotropic glutamate receptor agonist (1S, 3R)-1-aminocyclopentane-1, 3-dicarboxylic acid (1S, 3R-ACPD) produced
similar bi-directional actions on the cyclic AMP formation. Both of these inhibitory and facilitatory actions of NS-105 and
1S, 3R-ACPD were blocked by L(+)-2-amino-3-phosphopropinoic acid (L-AP3). NS-105 (10–6 M) and 1S, 3R-ACPD (10–4 M) significantly enhanced isoproterenol- and adenosine-stimulated cyclic AMP formation. The enhancement of such Gs-coupled
receptor agonists-stimulated cyclic AMP formation was also produced by quisqualate but not by L(+)-2-amino-4-phosphonobutanoate
(L-AP4). The phosphoinositides hydrolysis was enhanced by 1S, 3R-ACPD (10–4 M) but not by NS-105 (10–6 M), however, 1S, 3R-ACPD-induced increase in phosphoinositides turnover was attenuated by NS-105. These findings suggest
that NS-105 stimulates metabotropic glutamate receptor subclasses that are coupled both negatively and positively to adenylate
cyclase, but it acts as an antagonist at the receptor subclasses that are linked to phosphoinositides hydrolysis.
Received: 3 February 1997 / Accepted: 25 April 1997 相似文献
12.
Hisashi Tanii Norio Taniguchi Hisayoshi Niigawa Takayoshi Hosono Yasumitsu Ikura Sakae Sakamoto Takashi Kudo Tsuyoshi Nishimura Masatoshi Takeda 《Brain research》1996,743(1-2)
The neuroleptic malignant syndrome (NMS) is a life-threatening complication of neuroleptic treatment. To elucidate the pathogenesis of NMS, an animal model has been developed. Experimental rabbits treated with haloperidol (1 mg/kg) by intramuscular injection, were studied for the diagnostic symptoms of increased muscle rigidity, elevated body temperature, and high serum creatine phosphokinase (CPK) level. Administration of haloperidol (1 mg/kg) and atropine (0.4 mg/kg), and exposure to high ambient temperature (35°C) induced a significant increase in electromyographic activity with muscle rigidity similar to that observed in patients with NMS. Such rabbits also showed elevated body temperature and serum CPK value. In addition to the similarity of the signs and symptoms, all parameters measured (muscle rigidity, body temperature, and serum CPK level) were normalized by dantrolene treatment. The effectiveness of dantrolene in the experimental animal partially confirms the validity of this animal model for NMS. This experimental animal model for NMS may be useful to elucidate the pathogenesis of NMS. 相似文献
13.
New sonographic techniques for the diagnosis and treatment of hepatocellular carcinoma 总被引:1,自引:0,他引:1
Masatoshi Kudo 《Hepatology research》2007,37(S2):S193-S199
Ultrasound (US) contrast agents such as Levovist and Sonazoid are now commercially available in Japan. Innovative contrast agents and ultrasound technologies have dramatically changed both diagnostic and treatment strategies for hepatocellular carcinoma (HCC). Contrast-enhanced US is extremely useful in the differential diagnosis of hepatic tumors as well as in evaluation of post-treatment response of HCC after lipiodol transarterial chemoembolization and radio frequency ablation. Harmonic US sensitively detects residual cancer cells in HCC patients after treatment, to facilitate accurate guidance for needle insertion for US monitoring; no other imaging modalities, including computed tomography (CT) or magnetic resonance imaging (MRI), have such capability. In 2005, the breakthrough technology of pure arterial phase imaging, which depicts only intranodular arterial accumulated maximum intensity projection images, was developed from advanced raw data storing and accumulation technologies. This technique can clearly identify whether blood supplyin the tumor is of arterial or portal origin, to facilitate the non-invasive characterization of nodular lesions associated with liver cirrhosis. Again, CT or MRI do not have such capabilities. This innovative technique can help differentiate premalignant lesions from overt HCC. Concurrent real-time imaging of multi-detector CT and US, known as real-time virtual sonography, has recently become available. This technique greatly facilitates the treatment guidance for HCC. These newly introduced sonographic techniques are dramatically changing the diagnostic and therapeutic strategies for HCC, which are expected to improve the prognosis of HCC patients. 相似文献
14.
Yusen Chen Jun Nakura Jing-Ji Jin Zhihong Wu Miyuki Yamamoto Michiko Abe Yasuharu Tabara Yoshikuni Yamamoto Michiya Igase Xiao Bo Katsuhiko Kohara Tetsuro Miki 《Hypertension research》2003,26(6):439-444
The beta-adrenoceptor (beta-AR)-stimulatory guanine nucleotide-binding (Gs) protein system has been shown to play important roles in the cardiovascular system. The gene encoding the alpha-subunit of Gs proteins (GNAS1) is a candidate genetic determinant for hypertension. Because alcohol consumption is known to affect blood pressure partly through the beta-AR-Gs protein system, we examined the possible interaction between GNAS1 T393C polymorphism and drinking status in the association with hypertension in the present study. As a result, a non-significant but reasonable trend supporting the presence of an interaction was shown (p = 0.076). In line with this trend, the T393C polymorphism significantly interacted with drinking status in the association with systolic blood pressure (p = 0.028). Moreover, supporting the presence of an interaction, T allele carriers consistently had a higher probability of hypertension, higher systolic blood pressure, and higher diastolic blood pressure than CC homozygotes in non-drinkers and light drinkers. In contrast, CC homozygotes consistently had a higher probability of hypertension, higher systolic blood pressure, and higher diastolic blood pressure than T allele carriers in moderate to heavy drinkers. The present study also showed a significant interaction between the T393C polymorphism and drinking status in the association with pulse pressure (p = 0.026), reflected by a significant association between the T393C polymorphism and pulse pressure in moderate to heavy drinkers (p = 0.026). These findings may be helpful in conducting further molecular and biological studies on the relationship among the effects of alcohol, the beta-AR-Gs protein system, and hypertension. 相似文献
15.
Yoshitaka Hirooka Yoshikuni Kimura Masatsugu Nozoe Yoji Sagara Koji Ito Kenji Sunagawa 《Hypertension research》2006,29(1):49-56
Amlodipine is a dihydropyridine calcium channel blocker that is widely used for the treatment of hypertensive patients and has an antioxidant effect on vessels in vitro. The aim of the present study was to examine whether treatment with amlodipine reduced oxidative stress in the brains of stroke-prone spontaneously hypertensive rats (SHRSP). The animals received amlodipine, nicardipine or hydralazine for 30 days in their drinking water. Levels of thiobarbituric acid-reactive substances (TBARS) in the brain (cortex, cerebellum, hypothalamus, and brainstem) were measured before and after each treatment. Systolic blood pressure decreased to similar levels in the amlodipine-, nicardipine-, and hydralazine-treated groups. Urinary norepinephrine excretion was significantly reduced in SHRSP after treatment with amlodipine, but not with nicardipine or hydralazine. Levels of TBARS in the cortex, cerebellum, hypothalamus, and brainstem were significantly higher in SHRSP than in Wistar-Kyoto rats (WKY), and were reduced in amlodipine-treated, but not in nicardipine- or hydralazine-treated, SHRSP. Electron spin resonance spectroscopy revealed increased levels of reactive oxygen species in the brains of SHRSP, which were reduced by treatment with amlodipine. Intracisternal infusion of amlodipine also reduced systolic blood pressure, urinary norepinephrine excretion, and the levels of TBARS in the brain. These results suggested that oxidative stress in the brain was enhanced in SHRSP compared with WKY rats. In addition, antihypertensive treatment with amlodipine reduced oxidative stress in all areas of the brain examined and decreased blood pressure without a reflex increase in sympathetic nerve activity in SHRSP. 相似文献
16.
Hisashi Kai Takahiro Mori Keisuke Tokuda Narimasa Takayama Nobuhiro Tahara Kiyoko Takemiya Hiroshi Kudo Yusuke Sugi Daisuke Fukui Hideo Yasukawa Fumitaka Kuwahara Tsutomu Imaizumi 《Hypertension research》2006,29(9):711-718
Oxidative stress is implicated in the pathogenesis of various cardiovascular diseases. We have shown that in Wistar rats with a suprarenal aortic constriction (AC), pressure overload-induced transient perivascular inflammation (monocyte chemoattractant protein-1 [MCP-1] induction and macrophage accumulation) in the early phase is the determinant of reactive myocardial fibrosis and resultant diastolic dysfunction in the late phase. Thus, we investigated the role of reactive oxygen species production in cardiac remodeling in AC rats. Superoxide production and the footprint of lipid peroxidation were assessed using dihydroethidium staining and immunohistostaining against 4-hydroxy-2-nonenal (4-HNE), respectively. In sham rats, dihydroethidium and 4-HNE signals were scarcely found in the heart. At day 3, AC rats showed dihydroethidium signals mainly in the intramyocardial arterial wall, whereas modest 4-HNE staining was observed diffusely in the myocardium. These signals declined to lower levels by day 14 despite sustained hypertension. Chronic administration of a subdepressor dose of an angiotensin II type 1 receptor blocker candesartan reduced the pressure overload-induced dihydroethidium and 4-HNE signals at day 3. Moreover, candesartan decreased MCP-1 induction and macrophage infiltration at day 3 and prevented myocardial fibrosis at day 14, without affecting left ventricle and myocyte hypertrophy. In conclusion, acute pressure overload induced self-limited superoxide production mainly in the vascular wall. The reactive oxygen species production would contribute to the perivascular inflammation and subsequent myocardial fibrosis. Angiotensin II was suggested to have a pressure-independent effect on the reactive oxygen species production. 相似文献
17.
Kazuo Yamakawa Masashi Takanashi Masao Watanabe Noriyuki Nakamura Tomonori Kobayashi Masato Hasegawa Yoshikuni Mizuno Shigeki Tanaka Hideo Mori 《Neuropathology》2006,26(6):586-591
We report on a male patient with Pick disease who had shown severe white matter atrophy and dilatation of the lateral ventricle in the frontal lobe from an early stage. Upon admission to our hospital 2 years after disease onset, the patient showed apathy, and MRI revealed severe atrophy of the cortex and white matter of the frontal lobe. He died at age 74, 11 years after disease onset. Autopsy revealed severe atrophy of the frontal and temporal lobes, severe loss of white matter in the frontal lobe, dilatation of the lateral ventricles, and cortical thinning. Histopathological examination showed severe loss of myelinated fibers in the frontal white matter and severe neuronal loss with gliosis in the frontal and temporal cortices. Many Pick bodies were seen. Our patient had a rare case of Pick disease predominantly affecting the frontal lobe with severe involvement of the white matter from an early stage. This case suggests that myelinated fibers in the white matter as well as cerebral neurons are primarily affected in Pick disease. 相似文献
18.
S Suzuki S Sakamoto H Kudo 《Rinsho byori. The Japanese journal of clinical pathology》1991,39(5):531-535
Thymidylate synthetase (TS) and thymidine kinase (TK) are know to catalyze the methylation of dUMP for the de novo synthesis of dTMP and the phosphorylation of thymidine for the salvage synthesis of dTMP in the pyrimidine pathway, respectively, and both enzyme activities are high in rapidly proliferating tissues. In the present study, these enzyme activities and the immunohistochemistry using monoclonal anti-bromodeoxyuridine (BrdU) were investigated during the period of proliferation of bone marrow cells after the hypoplastic period induced by cyclophosphamide (Cy) treatment in rats. Right after Cy treatment, nucleated cell count (NCC) of bone marrow cells, BrdU labelling ratio and TK activity were abruptly decreased. On the other hand, TS activity peaked at day 5 followed by an increase of TK activity, NCC and BrdU labelling ratio from day 7 after Cy treatment. These results indicate that, in the proliferation of bone marrow cells, the DNA de novo synthesis rises at first, and secondly, the DNA salvage synthesis predominantly increases with the increase of bone marrow cells labelled with BrdU, i.e., increase of the cells in the S phase. 相似文献
19.
20.
S. Kudo K. Umehara Yoshifumi Abe Masayuki Furukawa Masaaki Odomi 《Psychopharmacology》1997,131(4):388-393
To elucidate the penetrability of carteolol, a β-adrenoceptor antagonist (β-blocker) into the brain of rats, intracerebral
and serum concentrations of the compound were determined in male rats receiving single or repetitive oral administration of
carteolol hydrochloride at 30 mg/kg. The time-course of the intracerebral concentration of carteolol following single IV administration
of the compound at 10 and 30 mg/kg was also studied in male rats. A high-performance liquid chromatography method was used
to determine the intracerebral and serum concentrations. Following single oral dosing, the intracerebral concentration of
carteolol reached a maximum of 0.074 μg/g at 2 h postdosing and declined with a half-life of 3.7 h, and the Cmax and AUC of carteolol in the brain were 12.5% and 19.8% of those in serum. The intracerebral and serum concentrations of carteolol
were determined in male rats receiving repetitive oral dosing of the compound once daily for 7 days. The concentration of
carteolol in the brain and serum at 1 h postdosing varied within a range of 0.059–0.091 μg/g and 0.321–0.443 μg/ml, respectively,
throughout the dosing period, showing no changes in the penetrability of the compound into the brain due to repeated dosing.
The concentration of carteolol in the brain and serum increased in a dose-dependent manner in rats receiving a single IV administration
of the compound. The elimination half-life of carteolol in the serum and brain was 0.6–0.8 h and 1.3–1.7 h, respectively,
in rats following single IV dosing of the compound. The half-life in the brain was about twice as long as that in the serum.
The brain to serum concentration ratio was 0.306:0.499. From the above results, it was concluded that carteolol is distributed
from the circulation to the brain with low penetrability.
Received: 30 October 1996/Final version: 16 December 1996 相似文献