全文获取类型
收费全文 | 5953篇 |
免费 | 360篇 |
国内免费 | 34篇 |
专业分类
耳鼻咽喉 | 62篇 |
儿科学 | 90篇 |
妇产科学 | 80篇 |
基础医学 | 748篇 |
口腔科学 | 116篇 |
临床医学 | 354篇 |
内科学 | 1677篇 |
皮肤病学 | 158篇 |
神经病学 | 538篇 |
特种医学 | 252篇 |
外科学 | 932篇 |
综合类 | 24篇 |
预防医学 | 103篇 |
眼科学 | 82篇 |
药学 | 422篇 |
中国医学 | 28篇 |
肿瘤学 | 681篇 |
出版年
2023年 | 33篇 |
2022年 | 55篇 |
2021年 | 127篇 |
2020年 | 82篇 |
2019年 | 86篇 |
2018年 | 131篇 |
2017年 | 120篇 |
2016年 | 139篇 |
2015年 | 155篇 |
2014年 | 175篇 |
2013年 | 200篇 |
2012年 | 364篇 |
2011年 | 413篇 |
2010年 | 223篇 |
2009年 | 198篇 |
2008年 | 335篇 |
2007年 | 376篇 |
2006年 | 338篇 |
2005年 | 334篇 |
2004年 | 339篇 |
2003年 | 395篇 |
2002年 | 351篇 |
2001年 | 118篇 |
2000年 | 71篇 |
1999年 | 108篇 |
1998年 | 86篇 |
1997年 | 54篇 |
1996年 | 70篇 |
1995年 | 57篇 |
1994年 | 81篇 |
1993年 | 45篇 |
1992年 | 82篇 |
1991年 | 58篇 |
1990年 | 53篇 |
1989年 | 54篇 |
1988年 | 51篇 |
1987年 | 58篇 |
1986年 | 31篇 |
1985年 | 34篇 |
1984年 | 27篇 |
1983年 | 13篇 |
1982年 | 23篇 |
1981年 | 17篇 |
1980年 | 17篇 |
1979年 | 21篇 |
1977年 | 17篇 |
1975年 | 14篇 |
1974年 | 13篇 |
1973年 | 14篇 |
1970年 | 13篇 |
排序方式: 共有6347条查询结果,搜索用时 812 毫秒
991.
Kotani K Sakane N Saiga K Adachi S Shimohiro H Mu H Kurozawa Y 《Archives of medical research》2008,39(1):142-146
BACKGROUND: A-3826G polymorphism within the promoter region of the uncoupling protein-1 (UCP-1) gene is possibly involved in the pathophysiology of obesity and metabolic disorders. However, the effects of UCP-1 A-3826G polymorphism on high-density lipoprotein cholesterol (HDL-C), a major contributor to atherosclerotic disease, still have not been established. METHODS: A total of 298 healthy Japanese subjects (144 males and 154 females, mean age: 45.2 years) with a body mass index (BMI) of 20.0-30.0 kg/m(2), regular lifestyles, and receiving no medication were enrolled in the cross-sectional study to estimate the relationship of serum HDL-C levels with UCP-1 A-3826G polymorphism by genomic PCR and Bcl1-restriction fragment length polymorphism analysis. We used 1.04 mmol/L of HDL-C in Japanese males and 1.29 mmol/L in Japanese females as cut-off values of low HDL-cholesterolemia. RESULTS: The genotype and allele frequencies of UCP-1 A-3826G polymorphism were similar to those previously reported in the Japanese population. In males, HDL-C levels of the GG genotype (1.75+/-0.49 mmol/L) were significantly higher than those found in the AA genotype (1.45+/-0.34 mmol/L, p=0.015). In females, the occurrence rate of low HDL-cholesterolemia was significantly different by genotype: a low prevalence in the GG genotype (15.4% in the AA, 4.8% in the AG, 15.4% in the GG genotype, p=0.022). Logistic regression analysis was used to identify risk factors for low HDL-cholesterolemia, with adjustments for age, gender, smoking, alcohol intake, BMI, hypertriglyceridemia, and genotype. The GG genotype was detected as being a significant associated factor (odds ratio =0.11 [95% confidence interval =0.01-0.90], p=0.01), in addition to BMI and the presence of hypertriglyceridemia. CONCLUSIONS: These results suggest that the GG genotype may be an independent protective factor associated with low HDL-cholesterolemia in this population, although the role of the UCP-1 A-3826G polymorphism in HDL-C is complex and remains controversial. This hypothesis needs further investigation. 相似文献
992.
993.
Ueta H Shi C Miyanari N Xu XD Zhou S Yamashita M Ezaki T Matsuno K 《Hepatology (Baltimore, Md.)》2008,47(4):1352-1362
Donor dendritic cell (DC) migration and allosensitization in host secondary lymphoid organs after liver transplantation are ill defined. We used rat models to investigate graft-derived cells and intrahost allosensitization. Liver transplantation induced diffuse blood-borne migration of donor major histocompatibility class II antigen-positive (MHCII(+)) cells and MHCI(+) cells from the graft to host secondary lymphoid organs, not only the spleen, but also lymph nodes and Peyer's patches. The migrated MHCII(+) cells included DCs and some T cells and B cells. The DCs formed clusters with host BrdU(+) cells where they up-regulated CD86(+), and a CD8(+) T cell proliferative response originated within 24 hours after liver transplantation, demonstrating that these DCs can quickly mature and trigger direct allosensitization in host lymphoid organs. Transfer of allogeneic bone marrow cells also induced DC transmigration and a similar host response. In contrast, allogeneic thoracic duct lymph cells contained many fewer transmigrating DCs, and their transfer induced a comparable T cell response but significantly weaker CD8(+) T cell proliferation. Thus, there is a different outcome via the indirect pathway by host DCs that have captured donor alloantigens. Conclusion: The rat liver as well as bone marrow contains an immature DC population that can systemically transmigrate through blood vessel walls of the host secondary lymphoid organs, quickly mature, and induce diffuse intrahost CD8(+) T cell responses, which may promote graft rejection. 相似文献
994.
Sato N Jitsuoka M Shibata T Hirohashi T Nonoshita K Moriya M Haga Y Sakuraba A Ando M Ohe T Iwaasa H Gomori A Ishihara A Kanatani A Fukami T 《Journal of medicinal chemistry》2008,51(15):4765-4770
(9S)-9-(2-Hydroxy-4,4-dimethyl-6-oxo-1-cyclohexen-1-yl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one ((S)-1) was identified as a selective and orally active neuropeptide Y Y5 receptor antagonist. The structure-activity relationship for this structural class was investigated and showed that limited substitution on the phenyl ring was tolerated and that modification of the 4,4-dimethyl group of the cyclohexenone and the 3,3-dimethyl group of the xanthenone parts slightly improved potency. The plasma concentration-time profile after oral administration of (S)-1 in Sprague-Dawley (SD) rats showed significant in vivo racemization of (S)-1 and that (S)-1 is cleared much more quickly than (R)-1. The duration of (S)-1 in SD rats after oral administration of (RS)-1 racemate was twice as long as that following oral administration of (S)-1. The C max values of (S)-1 after administration of (S)-1 and (RS)-1 were comparable, and the brain to plasma ratio for (S)-1 was 0.34 in SD rats. In our acute D-Trp (34)NPY-induced food intake model, both (S)-1 and (RS)-1 showed potent and dose-dependent efficacy. Therefore, the use of (RS)-1 is suitable for studies that require sustained plasma exposure of (S)-1. 相似文献
995.
Motani K Tabata K Kimura Y Okano S Shibata Y Abiko Y Nagai H Akihisa T Suzuki T 《Biological & pharmaceutical bulletin》2008,31(4):618-626
Neuroblastoma is the most common solid tumor in children. Despite aggressive chemotherapy, the prognosis of patients with advanced neuroblastoma is still very poor. Our recent study showed that xanthoangelol, a major chalcone constituent of the stem exudates of Angelica keiskei, induced caspase-3-dependent apoptosis in neuroblastoma cells. However, details of the mechanism underlying its apoptotic action are still unclear. Here we show that xanthoangelol triggers oxidative stress by generation of reactive oxygen species and induces apoptosis through release of cytochrome c and activation of caspase-9 in IMR-32 cells. Pretreatment with an antioxidant, vitamin E, prevented the increase of reactive oxygen species and apoptosis induced by xanthoangelol. Proteomic analysis using 2-dimensional electrophoresis and MALDI-TOF-MS revealed that DJ-1 protein was involved in xanthoangelol-induced apoptosis. DJ-1 responded to its oxidative stress status by being oxidized itself. Furthermore, DJ-1 was down-regulated by xanthoangelol, leading to loss of antioxidant function and acceleration of apoptosis. We also show that xanthoangelol has a cytotoxic effect on drug-resistant LA-N-1 and NB-39 cells as well as drug-sensitive IMR-32 and SK-N-SH cells. These findings suggest that xanthoangelol induces apoptosis by increasing reactive oxygen species and targeting DJ-1, and such mechanism may be an effective therapeutic approach for advanced neuroblastoma. 相似文献
996.
Kohda Y Shirakawa H Yamane K Otsuka K Kono T Terasaki F Tanaka T 《The Journal of toxicological sciences》2008,33(4):459-472
Diabetic cardiomyopathy can progress toward overt heart failure with increased mortality. The hexosamine biosynthesis pathway has been implicated in signaling for fibrosis by the kidney. Thiamine (vitamin B(1)) is an indispensable coenzyme and required at intracellular glucose metabolism. In this study, we assessed if decrease of flux through the hexosamine biosynthesis pathway induced by high-dose thiamine therapy counteracts diabetes-induced cardiac fibrosis. The diabetes model used was the streptozotocin-induced diabetic rat. Normal control and diabetic rats were studied for 2 weeks with and without thiamine, and followings were analyzed; plasma biochemicals (total cholesterol and triglycerides), morphological changes, mRNA abundance relevant to cardiac failure (brain natriuretic peptide) and fibrosis (transforming growth factor-beta1, thrombospondine, fibronectin, plasminogen activator-I and connective tissue growth factor) as well as and matrix metalloproteinase activity were investigated. Thiamine repletion prevented diabetes-induced cardiac fibrosis without changes in plasma glucose concentration. This was achieved by prevention of thiamine depletion, increased pro-fibrotic mRNA abundance and decreased metalloproteinase activity in the heart of diabetic rats. O-glycosylated protein was significantly higher in the left ventricular of diabetic rats compared to control rats, which was decreased by thiamine administration. Thiamine repletion prevented diabetes-induced cardiac fibrosis in experimental diabetes, probably by suppression of hexosamine biosynthesis pathway. 相似文献
997.
Yoshizumi T Takahashi H Miyazoe H Sugimoto Y Tsujita T Kato T Ito H Kawamoto H Hirayama M Ichikawa D Azuma-Kanoh T Ozaki S Shibata Y Tani T Chiba M Ishii Y Okuda S Tadano K Fukuroda T Okamoto O Ohta H 《Journal of medicinal chemistry》2008,51(13):4021-4029
A series of compounds based on 7-{[4-(2-methylphenyl)piperidin-1-yl]methyl}-6,7,8,9-tetrahydro-5 H-cyclohepta[ b]pyridine-9-ol ( (-)-8b), a potent and selective opioid receptor-like 1 (ORL1) antagonist, was prepared and evaluated using structure-activity relationship studies with the aim of removing its affinity to human ether-a-go-go related gene (hERG) K (+) channel. From these studies, 10l was identified as an optimized structure with respect to ORL1 antagonist activity, and affinity to the hERG K (+)channel. Furthermore, 10l showed good in vivo antagonism with a wide therapeutic index in regards to adverse cardiovascular effects. 相似文献
998.
Doi Yuji Wakana Daigo Kitaoka Satoshi Sato Fumiaki Tanaka Eiji Takeda Hisashi Hosoe Tomoo 《Journal of natural medicines》2023,77(2):306-314
Journal of Natural Medicines - The genus Claviceps (Clavicipitaceae) is famous for producing ergot alkaloids (EAs) in sclerotia. EAs can cause ergotism, resulting in convulsions and necrosis when... 相似文献
999.
Kasahara S Hara T Tsurumi H Goto N Kanemura N Yoshikawa T Yamada T Sawada M Takahashi T Moriwaki H 《The Japanese journal of antibiotics》2008,61(3):115-121
BACKGROUND: Recent advances in the treatment of hematological malignancies often induce febrile neutropenia (FN) due to severe myelosuppression. The aim of this study was to evaluate the safety and efficacy of biapenem in such FN. METHODS: Candidate patients were admitted to our hospital and were treat of their hematological malignancy from February 2005 to March 2006. They gave written informed consent to enter this study in advance. When the diagnosis of FN was established among them, those patients received intravenous biapenem 0.6 g every 12 hours. This trail was approved by our institutional review board. RESULTS: A total of 54 consecutive patients were registered and 49 patients were evaluable for response. The median age was 61. The underlying diseases were acute lymphocytic leukemia in 6 cases, acute myelocytic leukemia in 21, multiple myeloma in 3, and non-Hodgkin's lymphoma in 19. The response rate was 78% (excellent response: 51%, good response: 27%, minor response: 6%, no response: 16%). In patients with neutrophil counts under 500/microl, the response rate was 73%. Infectious death or other serious adverse events were not observed. CONCLUSION: Biapenem is effective and safe for treating FN. 相似文献
1000.
Kazumichi Kawakubo Shunsuke Ohnishi Yutaka Hatanaka Kanako C. Hatanaka Hidetaka Hosono Yoshimasa Kubota Mako Kamiya Masaki Kuwatani Hiroshi Kawakami Yasuteru Urano Naoya Sakamoto 《Molecular imaging and biology》2016,18(3):463-471