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991.
Shinohara Y Toyohira Y Ueno S Liu M Tsutsui M Yanagihara N 《Biochemical pharmacology》2007,74(11):1608-1618
We report the effects of resveratrol, a polyphenol found in the skins of red grapes, on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. Resveratrol suppressed catecholamine secretion and (22)Na(+) and (45)Ca(2+) influx induced by acetylcholine, an agonist of nicotinic acetylcholine receptors, in a concentration-dependent manner (IC(50)=20.4, 11.0, and 62.8 microM, respectively). Resveratrol also inhibited catecholamine secretion induced by veratridine, an activator of voltage-dependent Na(+) channels, and 56 mM K(+), an activator of voltage-dependent Ca(2+) channels, at concentrations similar to those for (45)Ca(2+) influx. Resveratrol directly inhibited the current evoked by acetylcholine in Xenopus oocytes expressing alpha3beta4 neuronal nicotinic acetylcholine receptors (IC(50)=25.9 microM). Furthermore, resveratrol (IC(50)=5.32 microM) attenuated (14)C-catecholamine synthesis induced by acetylcholine. The present findings suggest that resveratrol inhibits acetylcholine-induced catecholamine secretion and synthesis through suppressing ion influx in cultured bovine adrenal medullary cells. 相似文献
992.
Takahashi S Iwai H Kosaka K Miyazaki T Osanai Y Arao N Tanaka K Nagai K Nakagawa A 《The Journal of antibiotics》2007,60(11):717-720
A novel melanogenesis inhibitor, byelyankacin (1), was isolated from the fermentation broth of a bacterial strain. The producing organism, designated B20, was identified as a member of the genus Enterobacter based on taxonomic characteristics. 1 was obtained as a white powder from the culture medium by solvent extraction and serial chromatographic purification. The structure of 1 was determined as (E)-4-(2-isocyanovinyl)phenyl alpha-L-rhamnopyranoside on the basis of spectroscopic data. 1 potently inhibited mushroom tyrosinase and melanogenesis of B16-2D2 melanoma cells with IC50 value of 2.1 nM and 30 nM, respectively. 相似文献
993.
Takuro Tobina Akira Kiyonaga Yuko Akagi Yukari Mori Kojiro Ishii Hitoshi Chiba Munehiro Shindo Hiroaki Tanaka 《Journal of Sports Science and Medicine》2007,6(2):220-226
Angiotensin I converting enzyme (ACE) gene Insertion / Deletion (I/D) polymorphism is associated with exercise trainability and exercise induced left ventricular hypertrophy. However, it is unclear whether this polymorphism influences exercise trainability in the elderly, and the electrocardiological alterations by exercise training is unknown among the genotypes. We herein investigated the association between ACE gene insertion/deletion (I/D) polymorphism, exercise trainability and the electrocardiological alternations by exercise in elderly women. Eighty four elderly women participated in this study. In all subjects the leg extension power (LEP) and lactate threshold (LT) were determined in order to evaluate the muscle strength, aerobic capacity and to also select the appropriate training intensity for each individual. They performed bench step exercise training for 12 weeks. A resting electrocardiogram was recorded for the obtained QTc interval in before and after the program. The baseline of aerobic capacity was higher in I/I than that in I/D, and the QTc interval was shorter in I/I than that in I/D. All other characteristics were similar among the genotypes. The QTc interval tended to be shorten only in the D/D. Furthermore, the value of the QTc interval change showed a significant difference between the I/I and D/D genotype after the program. The LT and LEP demonstrated a similar response among the genotypes. The D allele of ACE gene I/D polymorphism may therefore play a role in the electrocardiological aspect during exercise training, however, it was not found to influence the aerobic capacity.
Key points
- The D allele of ACE gene I/D polymorphism may play a role in the electrocardiological aspects during exercise training
- ACE gene I/D polymorphism was not determined the aerobic capacity and leg strength in elderly people.
- The ACE gene I/D polymorphism did not influence aerobic and strength trainability in elderly people.
994.
Knock-in of mutant K-ras in nontumorigenic human epithelial cells as a new model for studying K-ras mediated transformation 总被引:1,自引:0,他引:1
Konishi H Karakas B Abukhdeir AM Lauring J Gustin JP Garay JP Konishi Y Gallmeier E Bachman KE Park BH 《Cancer research》2007,67(18):8460-8467
The oncogenic function of mutant ras in mammalian cells has been extensively investigated using multiple human and animal models. These systems include overexpression of exogenous mutant ras transgenes, conditionally expressed knock-in mouse models, and somatic cell knockout of mutant and wild-type ras genes in human cancer cell lines. However, phenotypic discrepancies between knock-in mice and transgenic mutant ras overexpression prompted us to evaluate the consequences of targeted knock-in of an oncogenic K-ras mutation in the nontumorigenic human breast epithelial cell line MCF-10A and hTERT-immortalized human mammary epithelial cells. Our results show several significant differences between mutant K-ras knock-in cells versus their transgene counterparts, including limited phosphorylation of the downstream molecules extracellular signal-regulated kinase and AKT, minor proliferative capacity in the absence of an exogenous growth factor, and the inability to form colonies in semisolid medium. Analysis of 16 cancer cell lines carrying mutant K-ras genes indicated that 50% of cancer cells harbor nonoverexpressed heterozygous K-ras mutations similar to the expression seen in our knock-in cell lines. Thus, this system serves as a new model for elucidating the oncogenic contribution of mutant K-ras as expressed in a large fraction of human cancer cells. 相似文献
995.
996.
T Takahashi Y Saikawa T Igarashi S Tsuwano K Kumagai R Nakamura T Ooyama N Wada H Takeuchi H Takaishi Y Kitagawa 《Oncology letters》2010,1(4):673-677
Advanced gastric cancer frequently results in the inability to ingest food or drink orally, a condition called malignant gastrointestinal obstruction (MGO). MGO is clinically defined as a gastrointestinal outlet obstruction caused by a large tumor, or malignant bowel obstruction with peritoneal dissemination. MGO impacts the quality of life by interfering with oral intake and by causing gastrointestinal symptoms, such as nausea, vomiting and abdominal pain. Octreotide acetate (OA) is an analogue of somatostatin which has been increasingly used to relieve gastrointestinal symptoms since it decreases the secretion of digestive juices and increases the absorption of water and electrolytes. In Japan, the oral anticancer drug S-1 was recently adopted as a key chemotherapeutic agent in advanced gastric cancer; however, its oral formulation precludes its utility in the MGO setting. This is a pilot study of chemoradiotherapy plus OA in gastric cancer with MGO. Patients were initially treated with OA to control gastrointestinal symptoms. Following resolution of their symptoms, the patients received chemotherapy with S-1 plus low-dose cisplatin and radiation. Irradiation was targeted at the primary tumor and surrounding lesions, including the lymph nodes. Grade 4 toxicity was observed in only 1 patient, and no treatment-related deaths were noted. After treatment, 3 patients achieved a partial response and 4 achieved stable disease. Of the 9 patients, 8 were able to tolerate solid food orally and were discharged. The outcomes of these cases suggest that OA is a useful adjunctive therapy that enables advanced gastric cancer patients with MGO to receive S-1-containing chemotherapy. 相似文献
997.
Tea catechins with a galloyl moiety suppress postprandial hypertriacylglycerolemia by delaying lymphatic transport of dietary fat in rats 总被引:6,自引:0,他引:6
Ikeda I Tsuda K Suzuki Y Kobayashi M Unno T Tomoyori H Goto H Kawata Y Imaizumi K Nozawa A Kakuda T 《The Journal of nutrition》2005,135(2):155-159
Tea catechins, (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), and (-)-epigallocatechin gallate (EGCG), have been shown to be epimerized to (-)-catechin (C), (-)-gallocatechin (GC), (-)-catechin gallate (CG), and (-)-gallocatechin gallate (GCG), respectively, during heat treatment. In this study, we examined the effect of tea catechins rich in ECG and EGCG and heat-treated tea catechins rich in CG and GCG on postprandial hypertriacylglycerolemia in rats. Both tea catechins and heat-treated tea catechins suppressed postprandial hypertriacylglycerolemia. Lymphatic recovery of (14)C-trioleoylglycerol in rats cannulated in the thoracic duct was delayed by the administration of tea catechins and heat-treated tea catechins. Tea catechins and heat-treated tea catechins had the same effect on all variables tested. These catechin preparations dose-dependently inhibited the activity of pancreatic lipase in vitro. When purified catechins were used, only those with a galloyl moiety inhibited the activity of pancreatic lipase. These results suggest that catechins with a galloyl moiety suppress postprandial hypertriacylglycerolemia by slowing down triacylglycerol absorption through the inhibition of pancreatic lipase. Because postprandial hypertriacylglycerolemia is a risk factor for coronary heart disease, our results suggest that catechins with a galloyl moiety may prevent this disease. 相似文献
998.
Mizuho Nosaka Yuko Ishida Akihiko Kimura Toshikazu Kondo 《International journal of legal medicine》2010,124(5):439-444
We immunohistochemically examined the expression of matrix metalloproteinase (MMP)-2 and MMP-9 using venous thrombi developed
by ligation of the inferior vena cava (IVC) in mice. Both MMP-2- and MMP-9- positive cells could be detected in the whole
course of thrombus formation after IVC ligation. Morphometrically, their number was greatest 14 days after IVC ligation and
thereafter, gradually decreased at 21 days. The number of MMP-9-positive cells was significantly higher than that of MMP-2-positive
cells at 1 to 7 days. The average ratio of MMP-9 to MMP-2 (MMP-9/MMP-2 ratio) was >2.0 in all thrombus samples at 1–5 days.
After 7 days, the MMP-9/MMP-2 ratio was less than 2.0. These observations implied that an MMP-9/MMP-2 ratio markedly exceeding
2.0 strongly indicates an age of 5 days or less. Furthermore, an MMP-9/MMP-2 ratio of <2.0 probably indicates an age of more
than 7 days. The present study demonstrated that the immunohistochemical detection of intrathrombotic MMP-2 and MMP-9 was
suitable to estimate the age of venous thrombi. 相似文献
999.
Shuko Tachibana Yuko Fujimaki Hiroyuki Yokoyama Osamu Okazaki Ken-ichi Sudo 《Drug metabolism and disposition》2005,33(11):1628-1636
Human cytochrome P450 (P450) isozyme(s) responsible for metabolism of the calmodulin antagonist 3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate (DY-9760e) and kinetic profiles for formation of its six primary metabolites [M3, M5, M6, M7, M8, and DY-9836 (3-[2-[4-(3-chloro-2-methylphenyl)piperazinyl]ethyl]-5,6-dimethoxyindazole)] were identified using human liver microsomes and recombinant P450 enzymes. In vitro experiments, including an immunoinhibition study, correlation analysis, and reactions with recombinant P450 enzymes, revealed that CYP3A4 is the primary P450 isozyme responsible for the formation of the DY-9760e metabolites, except for M5, which is metabolized by CYP2C9. Additionally, at clinically relevant concentrations, CYP2C8 and 2C19 make some contribution to the formation of M3 and M5, respectively. The formation rates of DY-9760e metabolites except for M8 by human liver microsomes are not consistent with a Michaelis-Menten kinetics model, but are better described by a substrate inhibition model. In contrast, the enzyme kinetics for all metabolites formed by recombinant CYP3A4 can be described by an autoactivation model or a mixed model of autoactivation and biphasic kinetics. Inhibition of human P450 enzymes by DY-9760e in human liver microsomes was also investigated. DY-9760e is a very potent competitive inhibitor of CYP2C8, 2C9 and 2D6 (Ki 0.25-1.7 microM), a mixed competitive and noncompetitive inhibitor of CYP2C19 (Ki 2.4 microM) and a moderate inhibitor of CYP1A2 and 3A4 (Ki 11.4-20.1 microM), suggesting a high possibility for human drug-drug interaction. 相似文献
1000.
Yamamoto Hiroki Takayasu Tatsunori Ishida Yuko Nosaka Mizuho Hata Satoshi Kuninaka Yumi Shimada Emi Hashizume Yumiko Ishigami Akiko Ozaki Mitsunori Kawaguchi Mariko Kimura Akihiko Furukawa Fukumi Kondo Toshikazu 《International journal of legal medicine》2020,134(3):997-1002
International Journal of Legal Medicine - This paper presents an unusual complex suicide case that died of nicotine addiction. The deceased was a 40-year-old male who was found lying dead on the... 相似文献