全文获取类型
收费全文 | 8113篇 |
免费 | 591篇 |
国内免费 | 55篇 |
专业分类
耳鼻咽喉 | 35篇 |
儿科学 | 176篇 |
妇产科学 | 165篇 |
基础医学 | 1368篇 |
口腔科学 | 191篇 |
临床医学 | 802篇 |
内科学 | 1805篇 |
皮肤病学 | 234篇 |
神经病学 | 938篇 |
特种医学 | 215篇 |
外科学 | 848篇 |
综合类 | 25篇 |
一般理论 | 5篇 |
预防医学 | 526篇 |
眼科学 | 113篇 |
药学 | 614篇 |
中国医学 | 10篇 |
肿瘤学 | 689篇 |
出版年
2024年 | 18篇 |
2023年 | 130篇 |
2022年 | 236篇 |
2021年 | 393篇 |
2020年 | 246篇 |
2019年 | 296篇 |
2018年 | 294篇 |
2017年 | 248篇 |
2016年 | 267篇 |
2015年 | 265篇 |
2014年 | 378篇 |
2013年 | 433篇 |
2012年 | 677篇 |
2011年 | 611篇 |
2010年 | 356篇 |
2009年 | 345篇 |
2008年 | 527篇 |
2007年 | 478篇 |
2006年 | 485篇 |
2005年 | 460篇 |
2004年 | 393篇 |
2003年 | 363篇 |
2002年 | 316篇 |
2001年 | 69篇 |
2000年 | 45篇 |
1999年 | 58篇 |
1998年 | 66篇 |
1997年 | 53篇 |
1996年 | 36篇 |
1995年 | 39篇 |
1994年 | 23篇 |
1993年 | 18篇 |
1992年 | 25篇 |
1991年 | 13篇 |
1990年 | 12篇 |
1989年 | 8篇 |
1988年 | 10篇 |
1987年 | 11篇 |
1986年 | 6篇 |
1985年 | 10篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1980年 | 2篇 |
1979年 | 4篇 |
1977年 | 7篇 |
1907年 | 2篇 |
1906年 | 3篇 |
1905年 | 3篇 |
1904年 | 2篇 |
1903年 | 4篇 |
排序方式: 共有8759条查询结果,搜索用时 15 毫秒
101.
Total administered dose of ibandronate determines its effects on bone mass and architecture in ovariectomized aged rats 总被引:2,自引:0,他引:2
OBJECTIVE: Ibandronate is a highly potent nitrogen-containing bisphosphonate that can prevent bone loss in various animal models as well as in clinical trials. We evaluated the effects of different doses and treatment schedules in ovariectomized aged rats, a model of human osteoporosis. METHODS: Eight-month-old female Wistar rats were ovariectomized or sham operated (n = 15/group). Doses of 0.1 to 30 microg/kg/day ibandronate were administered subcutaneously over a period of 20 weeks with or without a 5 times higher single loading dose starting one day postsurgery. In a subsequent experiment, the optimal preventive dose, which is the lowest dose that prevented bone loss completely, or a suboptimal preventive dose were administered over the same period, either daily or by 3 cyclical intermittent regimens (on/off weeks = 1/2, 1/4, and 1/6), resulting in the same cumulative total dose. RESULTS: Ovariectomy induced significant bone loss in the following primary endpoints: femoral radiographic density, dry weight/tissue volume, and calcium content/tissue volume. Histomorphometry in the tibia resulted in reduced trabecular bone mass, thickness, and number, and increased separation. The optimal dose was 1.0 microg/kg/day, while 0.1 microg/kg/day was suboptimal. Higher doses resulted in a plateau. The loading dose had no effect on the results. Cyclical intermittent administration dose-dependently prevented bone loss, providing equivalent results per total dose, irrespective of the administration schedule. CONCLUSION: There were no differences between the various regimens, suggesting that it is the total dose of ibandronate rather than the treatment schedule that is important for efficacy, at least within the tested dosing intervals. 相似文献
102.
103.
104.
Diem‐Lan Vu Julie‐Anne Dayer Stavroula Masouridi‐Levrat Christophe Combescure Elsa Boely Nina Khanna Nicolas J. Mueller Martina Kleber Michael Medinger JOERG Halter Jakob Passweg Antonia M. Müller Urs Schanz Yves Chalandon Dionysios Neofytos Christian van Delden Laurent Kaiser 《Transplant infectious disease》2020,22(4)
105.
106.
D?rthe Malzahn Martina Müller-Nurasyid Iris M Heid H-Erich Wichmann the KORA study group Heike Bickeb?ller 《European journal of human genetics : EJHG》2014,22(10):1217-1224
Among the single-nucleotide polymorphisms (SNPs) previously reported to be associated with body mass index (BMI) and obesity, we focus on a common risk variant rs7566605 upstream of the insulin-induced gene 2 (INSIG2) gene and a rare protective variant rs2229616 on the melanocortin-4 receptor (MC4R) gene. INSIG2 is involved in adipogenesis and MC4R effects hormonal appetite control in response to the amount of adipose tissue. The influence of rs2229616 (MC4R) on BMI and obesity has been confirmed repeatedly and insight into the underlying mechanism provided. However, a main effect of rs7566605 (INSIG2) is under debate because of inconsistent replications of association. Interaction of rs7566605 with age may offer an explanation. SNP–age and SNP–SNP interaction models were tested on independent individuals from three population-based longitudinal cohorts, restricting the analysis to an observed age of 25–74 years. KORA S3/F3, KORA S4/F4 (Augsburg, Germany, 1994–2005, 1999–2008), and Framingham-Offspring data (Framingham, USA, 1971–2001) were analysed, with a total sample size of N=6926 in the joint analysis. The effect of interaction between rs7566605 and age on BMI and obesity status is significant and consistent across studies. This new evidence for rs7566605 (INSIG2) complements previous research. In addition, the interaction effect of rs7566605 with the MC4R variant rs2229616 on BMI was observed. This effect size was three times larger than that in a previously reported single-locus main effect of rs2229616. This leads to the conclusion that SNP–age or SNP–SNP interactions can mask genetic effects for complex diseases if left unaccounted for. 相似文献
107.
Andrea E. Steuer Justine Raeber Christian Steuer Martina I. Boxler Dario A. Dornbierer Oliver G. Bosch Boris B. Quednow Erich Seifritz Thomas Kraemer 《Drug testing and analysis》2019,11(6):813-823
Gamma‐hydroxybutyrate (GHB) is a short‐chain fatty acid that occurs naturally in the mammalian brain and is prescribed as a medication against narcolepsy or used as a drug of abuse. Particularly, its use as a knock‐out drug in cases of drug‐facilitated crimes is of major importance in forensic toxicology. Because of its rapid metabolism and resulting narrow detection windows (<12 hours in urine), detection of GHB remains challenging. Thus, there is an urgent call for new markers to improve the reliable detection of GHB use. In the framework of a randomized, placebo‐controlled, crossover study in 20 healthy male volunteers, urine samples obtained 4.5 hours post‐administration were submitted to untargeted mass spectrometry [MS, quadrupole time of flight (QTOF)] analysis to identify possible new markers of GHB intake. MS data from four different analytical methods (reversed phase and hydrophilic interaction liquid chromatography; positive and negative electrospray ionization) were filtered for significantly changed features applying univariate and multivariate statistics. From the resulting 42 compounds of interest, 8 were finally identified including conjugates of GHB with carnitine, glutamate, and glycine as well as the endogenous compounds glycolate and succinylcarnitine. While GHB conjugates were only detectable in the GHB, but not in the placebo group, glycolate and succinylcarnitine were present in both groups albeit significantly increased through GHB intake. Untargeted metabolomics proved as a suitable tool for the non‐hypothesis driven identification of new GHB markers. However, more studies on actual concentrations, detection windows, and stability will be necessary to assess the suitability of these markers for routine application. 相似文献
108.
David Fern ndez-Ramos Fernando Lopitz-Otsoa Laura Delacruz-Villar Jon Bilbao Martina Pagano Laura Mosca Maider Bizkarguenaga Marina Serrano-Macia Mikel Azkargorta Marta Iruarrizaga-Lejarreta Jes s Sot Darya Tsvirkun Sebastiaan Martijn van Liempd Felix M Goni Cristina Alonso Mar a Luz Mart nez-Chantar Felix Elortza Liat Hayardeny Shelly C Lu Jos M Mato 《World journal of gastroenterology : WJG》2020,26(34):5101-5117
BACKGROUND Arachidyl amido cholanoic acid(Aramchol) is a potent downregulator of hepatic stearoyl-CoA desaturase 1(SCD1) protein expression that reduces liver triglycerides and fibrosis in animal models of steatohepatitis. In a phase IIb clinical trial in patients with nonalcoholic steatohepatitis(NASH), 52 wk of treatment with Aramchol reduced blood levels of glycated hemoglobin A1c, an indicator of glycemic control.AIM To assess lipid and glucose metabolism in mouse hepatocytes and in a NASH mouse model [induced with a 0.1% methionine and choline deficient diet(0.1 MCD)] after treatment with Aramchol.METHODS Isolated primary mouse hepatocytes were incubated with 20 μmol/L Aramchol or vehicle for 48 h. Subsequently, analyses were performed including Western blot, proteomics by mass spectrometry, and fluxomic analysis with ~(13)C-uniformly labeled glucose. For the in vivo part of the study, male C57 BL/6 J mice were randomly fed a control or 0.1 MCD for 4 wk and received 1 or 5 mg/kg/d Aramchol or vehicle by intragastric gavage for the last 2 wk. Liver metabolomics were assessed using ultra-high-performance liquid chromatography-time of flight-MS for the determination of glucose metabolism-related metabolites.RESULTS Combination of proteomics and Western blot analyses showed increased AMPK activity while the activity of nutrient sensor mTORC1 was decreased by Aramchol in hepatocytes. This translated into changes in the content of their downstream targets including proteins involved in fatty acid(FA) synthesis and oxidation [PACCα/β(S79), SCD1, CPT1A/B, HADHA, and HADHB], oxidative phosphorylation(NDUFA9, NDUFB11, NDUFS1, NDUFV1, ETFDH, and UQCRC2), tricarboxylic acid(TCA) cycle(MDH2, SUCLA2, and SUCLG2), and ribosome(P-p70S6K[T389] and P-S6[S235/S236]). Flux experiments with ~(13)C uniformely labeled glucose showed that TCA cycle cataplerosis was reduced by Aramchol in hepatocytes, as indicated by the increase in the number of rounds that malate remained in the TCA cycle. Finally, liver metabolomic analysis showed that glucose homeostasis was improved by Aramchol in 0.1 MCD fed mice in a dose-dependent manner, showing normalization of glucose, G6P, F6P, UDP-glucose, and Rbl5 P/Xyl5 P.CONCLUSION Aramchol exerts its effect on glucose and lipid metabolism in NASH through activation of AMPK and inhibition of mTORC1, which in turn activate FA β-oxidation and oxidative phosphorylation. 相似文献
109.
Renata Mojzikova Pavla Koralkova Dusan Holub Zuzana Zidova Dagmar Pospisilova Jaroslav Cermak Zuzana Striezencova Laluhova Karel Indrak Martina Sukova Martina Partschova Jana Kucerova Monika Horvathova Vladimir Divoky 《British journal of haematology》2014,165(4):556-563
Pyruvate kinase (PK) deficiency is an iron‐loading anaemia characterized by chronic haemolysis, ineffective erythropoiesis and a requirement for blood transfusion in most cases. We studied 11 patients from 10 unrelated families and found nine different disease‐causing PKLR mutations. Two of these mutations ‐ the point mutation c.878A>T (p.Asp293Val) and the frameshift deletion c.1553delG (p.(Arg518Leufs*12)) ‐ have not been previously described in the literature. This frameshift deletion was associated with an unusually severe phenotype involving neonatal hyperferritinaemia that is not typical of PK deficiency. No disease‐causing mutations in genes associated with haemochromatosis could be found. Inappropriately low levels of hepcidin with respect to iron loading were detected in all PK‐deficient patients with increased ferritin, confirming the predominant effect of accelerated erythropoiesis on hepcidin production. Although the levels of a putative hepcidin suppressor, growth differentiation factor‐15, were increased in PK‐deficient patients, no negative correlation with hepcidin was found. This result indicates the existence of another as‐yet unidentified erythroid regulator of hepcidin synthesis in PK deficiency. 相似文献
110.
Juraj Stanik Petra Dusatkova Ondrej Cinek Lucia Valentinova Miroslava Huckova Martina Skopkova Lenka Dusatkova Daniela Stanikova Mikulas Pura Iwar Klimes Jan Lebl Daniela Gasperikova Stepanka Pruhova 《Diabetologia》2014,57(3):480-484