全文获取类型
收费全文 | 1199篇 |
免费 | 133篇 |
专业分类
耳鼻咽喉 | 4篇 |
儿科学 | 11篇 |
妇产科学 | 15篇 |
基础医学 | 208篇 |
口腔科学 | 11篇 |
临床医学 | 190篇 |
内科学 | 188篇 |
皮肤病学 | 9篇 |
神经病学 | 127篇 |
特种医学 | 54篇 |
外科学 | 181篇 |
综合类 | 22篇 |
预防医学 | 130篇 |
眼科学 | 20篇 |
药学 | 87篇 |
肿瘤学 | 75篇 |
出版年
2023年 | 19篇 |
2021年 | 50篇 |
2020年 | 24篇 |
2019年 | 49篇 |
2018年 | 46篇 |
2017年 | 33篇 |
2016年 | 29篇 |
2015年 | 29篇 |
2014年 | 45篇 |
2013年 | 40篇 |
2012年 | 65篇 |
2011年 | 77篇 |
2010年 | 48篇 |
2009年 | 28篇 |
2008年 | 62篇 |
2007年 | 56篇 |
2006年 | 45篇 |
2005年 | 56篇 |
2004年 | 40篇 |
2003年 | 39篇 |
2002年 | 43篇 |
2001年 | 31篇 |
2000年 | 31篇 |
1999年 | 33篇 |
1998年 | 15篇 |
1997年 | 11篇 |
1996年 | 8篇 |
1995年 | 8篇 |
1994年 | 8篇 |
1993年 | 7篇 |
1992年 | 25篇 |
1991年 | 20篇 |
1990年 | 14篇 |
1989年 | 20篇 |
1988年 | 7篇 |
1987年 | 14篇 |
1986年 | 13篇 |
1984年 | 9篇 |
1983年 | 8篇 |
1980年 | 9篇 |
1979年 | 9篇 |
1978年 | 10篇 |
1977年 | 7篇 |
1976年 | 5篇 |
1975年 | 7篇 |
1974年 | 9篇 |
1973年 | 12篇 |
1972年 | 7篇 |
1971年 | 6篇 |
1970年 | 7篇 |
排序方式: 共有1332条查询结果,搜索用时 90 毫秒
1.
Megumi Oshima Brendon L. Neuen JingWei Li Vlado Perkovic David M. Charytan Dick de Zeeuw Robert Edwards Tom Greene Adeera Levin Kenneth W. Mahaffey Luca De Nicola Carol Pollock Norman Rosenthal David C. Wheeler Meg J. Jardine Hiddo J.L. Heerspink 《Journal of the American Society of Nephrology : JASN》2020,31(12):2925
2.
3.
Ping-Tao Tseng Chun-Pai Yang Kuan-Pin Su Tien-Yu Chen Yi-Cheng Wu Yu-Kang Tu Pao-Yen Lin Brendon Stubbs Andre F. Carvalho Yutaka J. Matsuoka Dian-Jeng Li Chih-Sung Liang Chih-Wei Hsu Yen-Wen Chen Yow-Ling Shiue 《Journal of pineal research》2020,69(2):e12663
Although exogenous melatonin supplementation has been suggested to be effective for episodic migraine prophylaxis, there is no conclusive evidence comparing the efficacy of exogenous melatonin supplementation to the other FDA-approved pharmacotherapy for episodic migraine prophylaxis. The aim of the current network meta-analysis (NMA) was to compare the efficacy of exogenous melatonin supplementation in patients with episodic migraine. The randomized placebo-controlled trials or randomized controlled trials (RCTs) incorporating a placebo in the study designs were included in our analyses. All of the NMA procedures were conducted under the frequentist model. The primary outcome was changes in frequency of migraine days and response rate after migraine prophylaxis with melatonin supplementation or pharmacological interventions. We included 25 RCTs in total with 4499 patients (mean age = 36.0 years, mean female proportion = 78.9%). The NMA demonstrated that migraine prophylaxis with oral melatonin 3 mg/d (immediate-release) at bedtime was associated with the greatest improvement in migraine frequency [mean difference = −1.71 days, 95% confidence interval (CI): −3.27 to −0.14 days compared to placebo] and the second highest response rate (odds ratio = 4.19, 95% CI = 1.46 to 12.00 compared to placebo). Furthermore, oral melatonin 3 mg (immediate-release) at bedtime was the most preferred pharmacological intervention among all of the investigated interventions when improvements in migraine frequency, response rate, dropout rate, and rates of any adverse events were taken into account. This pilot NMA suggests the potential prophylactic role of exogenous melatonin supplementation in patients with episodic migraine. 相似文献
4.
Warren Fiskus Christopher P. Mill Behnam Nabet Dimuthu Perera Christine Birdwell Taghi Manshouri Bernardo Lara Tapan M. Kadia Courtney DiNardo Koichi Takahashi Naval Daver Prithviraj Bose Lucia Masarova Naveen Pemmaraju Steven Kornblau Gautam Borthakur Guillermo Montalban-Bravo Guillermo Garcia Manero Sunil Sharma Matthew Stubbs Xiaoping Su Michael R. Green Cristian Coarfa Srdan Verstovsek Joseph D. Khoury Christopher R. Vakoc Kapil N. Bhalla 《Blood cancer journal》2021,11(5)
There is an unmet need to overcome nongenetic therapy-resistance to improve outcomes in AML, especially post-myeloproliferative neoplasm (MPN) secondary (s) AML. Studies presented describe effects of genetic knockout, degradation or small molecule targeted-inhibition of GFI1/LSD1 on active enhancers, altering gene-expressions and inducing differentiation and lethality in AML and (MPN) sAML cells. A protein domain-focused CRISPR screen in LSD1 (KDM1A) inhibitor (i) treated AML cells, identified BRD4, MOZ, HDAC3 and DOT1L among the codependencies. Our findings demonstrate that co-targeting LSD1 and one of these co-dependencies exerted synergistic in vitro lethality in AML and post-MPN sAML cells. Co-treatment with LSD1i and the JAKi ruxolitinib was also synergistically lethal against post-MPN sAML cells. LSD1i pre-treatment induced GFI1, PU.1 and CEBPα but depleted c-Myc, overcoming nongenetic resistance to ruxolitinib, or to BETi in post-MPN sAML cells. Co-treatment with LSD1i and BETi or ruxolitinib exerted superior in vivo efficacy against post-MPN sAML cells. These findings highlight LSD1i-based combinations that merit testing for clinical efficacy, especially to overcome nongenetic therapy-resistance in AML and post-MPN sAML.Subject terms: Acute myeloid leukaemia, Targeted therapies 相似文献
5.
6.
7.
OBJECTIVE: Prevotella intermedia has been reported to be associated with periodontal disease whilst P. nigrescens has predominantly been isolated from more specific conditions and healthy sites. The aim of the present study was to compare the enzyme activity of these species.
MATERIALS AND METHODS Nine strains of P. intermedio and 12 strains of P. nigrescens were studied. Lipolytic. saccharolytic, nucleolytic and proteolytic activity was determined by traditional microbiological and chromo-genic substrate methods.
RESULTS: All strains hydrolysed gelatine, casein. DNA and RNA. Lipase activity was produced by all strains except P. nigrescens ATCC 33563T . Lipolytic activity of P. nigrescens strains decreased as the environmental glucose concentration was increased. Only two strains, both P. intermedia , hydrolysed benzyl-arg-p-nitroanilide. All strains hydrolysed alkaline pnitrophenolphosphate (except P. intermedia DAL 100). produced glycylprolyl dipeptidase activity and demonstrated elastase-like activity. All but three strains (2 P. intermedia and I P. nigrescens) hydrolysed suc-ala-ala-pro-phe-p-nitroanilide. Overall, no qualitatively analysed enzyme activity was exclusive to all strains of either species. Quantitatively analysed activity exhibited a high degree of variability both within and between species.
CONCLUSIONS: P. intermedia and P. nigrescens degrade natural and synthetic substrates, but intra- and interspec-ies activity is variable. 相似文献
MATERIALS AND METHODS Nine strains of P. intermedio and 12 strains of P. nigrescens were studied. Lipolytic. saccharolytic, nucleolytic and proteolytic activity was determined by traditional microbiological and chromo-genic substrate methods.
RESULTS: All strains hydrolysed gelatine, casein. DNA and RNA. Lipase activity was produced by all strains except P. nigrescens ATCC 33563
CONCLUSIONS: P. intermedia and P. nigrescens degrade natural and synthetic substrates, but intra- and interspec-ies activity is variable. 相似文献
8.
9.
Alyssa M. Civantos Yasmeen Byrnes Changgee Chang Aman Prasad Kevin Chorath Seerat K. Poonia Carolyn M. Jenks Andrs M. Bur Punam Thakkar Evan M. Graboyes Rahul Seth Samuel Trosman Anni Wong Benjamin M. Laitman Brianna N. Harris Janki Shah Vanessa Stubbs Garret Choby Qi Long Christopher H. Rassekh Erica Thaler Karthik Rajasekaran 《Head & neck》2020,42(7):1597-1609
10.
Brendon Frank Yu-Ling Wei Kyung-Hoon Kim Abraham Guerrero Hervé Lebrec 《Journal of immunotoxicology》2018,15(1):119-125
The immunotoxic potential of drug candidates is assessed through the examination of results from a variety of studies and endpoints. While the functional assessment of CD8+ cytotoxic T-lymphocytes (CTL) is well-characterized in the clinic, the lack of a robust macaque CTL functional assay has been an important hurdle in evaluating and accurately quantifying cell-mediated CD8+ T-cell effector responses in the nonclinical setting. This paper describes the development of an assay to measure CTL activity in peripheral blood mononuclear cells (PBMC) isolated from Cynomolgus macaques. A human EGFR/CD3 Bispecific T-cell Engager (BiTE®) was used to mount a robust CD8+ T-cell response in the presence of target-expressing cells. Upon target engagement, degranulation of CD107a and production of interferon (IFN)-γ both reliably indicated a robust functional response in CD8+ T-cells. The BiTE®-mediated stimulation method proved to be favorable when compared to other methods of stimulation in the absence of target cells. These studies demonstrated acceptable longitudinal variability of the functional assay and sensitivity to dexamethasone-mediated immunosuppression. Taken together, the results indicated an assay leveraging CD3-bispecific antibodies and target-expressing cells can provide a robust approach to the in vitro or ex vivo assessment of CTL function in Cynomolgus macaques. Because the impairment of CTL activity by immunomodulators is recognized to be an important contributor to decreased antiviral defense and increased carcinogenicity risk, we believe that this novel assay to be a valuable addition to the immunotoxicology assessment of therapeutic drug candidates. 相似文献