全文获取类型
收费全文 | 70058篇 |
免费 | 4474篇 |
国内免费 | 266篇 |
专业分类
耳鼻咽喉 | 1109篇 |
儿科学 | 2014篇 |
妇产科学 | 1325篇 |
基础医学 | 7673篇 |
口腔科学 | 1450篇 |
临床医学 | 6905篇 |
内科学 | 14420篇 |
皮肤病学 | 1109篇 |
神经病学 | 6824篇 |
特种医学 | 2475篇 |
外国民族医学 | 5篇 |
外科学 | 12298篇 |
综合类 | 842篇 |
一般理论 | 94篇 |
预防医学 | 5812篇 |
眼科学 | 1367篇 |
药学 | 4514篇 |
中国医学 | 107篇 |
肿瘤学 | 4455篇 |
出版年
2023年 | 352篇 |
2022年 | 279篇 |
2021年 | 1613篇 |
2020年 | 928篇 |
2019年 | 1550篇 |
2018年 | 1811篇 |
2017年 | 1306篇 |
2016年 | 1338篇 |
2015年 | 1474篇 |
2014年 | 2274篇 |
2013年 | 3204篇 |
2012年 | 4852篇 |
2011年 | 5033篇 |
2010年 | 2760篇 |
2009年 | 2450篇 |
2008年 | 4451篇 |
2007年 | 4712篇 |
2006年 | 4569篇 |
2005年 | 4546篇 |
2004年 | 4289篇 |
2003年 | 3950篇 |
2002年 | 3659篇 |
2001年 | 552篇 |
2000年 | 472篇 |
1999年 | 587篇 |
1998年 | 642篇 |
1997年 | 538篇 |
1996年 | 466篇 |
1995年 | 507篇 |
1994年 | 493篇 |
1993年 | 418篇 |
1992年 | 370篇 |
1991年 | 376篇 |
1990年 | 307篇 |
1989年 | 289篇 |
1988年 | 280篇 |
1987年 | 261篇 |
1986年 | 272篇 |
1985年 | 366篇 |
1984年 | 430篇 |
1983年 | 360篇 |
1982年 | 513篇 |
1981年 | 483篇 |
1980年 | 449篇 |
1979年 | 205篇 |
1978年 | 272篇 |
1977年 | 255篇 |
1976年 | 200篇 |
1975年 | 219篇 |
1973年 | 183篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
71.
72.
73.
74.
75.
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
76.
Hajrunisa Cubro Karl A. Nath Sonja Suvakov Oscar Garcia-Valencia Santosh Parashuram Wendy M. White Tracey L. Weissgerber Meryl C. Nath Natasa M. Milic Fernando Sontag Livius V. d’Uscio Yi Zhu James L. Kirkland Tamar Tchkonia Mariam P. Alexander Reade A. Quinton Zvonimir S. Katusic Joseph P. Grande Vesna D. Garovic 《Kidney international》2021,99(3):646-656
77.
78.
Weiyu Ye Anna Olsson-Brown Robert A. Watson Vincent T. F. Cheung Robert D. Morgan Isar Nassiri Rosalin Cooper Chelsea A. Taylor Umair Akbani Oliver Brain Rubeta N. Matin Nicholas Coupe Mark R. Middleton Mark Coles Joseph J. Sacco Miranda J. Payne Benjamin P. Fairfax 《British journal of cancer》2021,124(10):1661
Background Immune checkpoint blockers (ICBs) activate CD8+ T cells, eliciting both anti-cancer activity and immune-related adverse events (irAEs). The relationship of irAEs with baseline parameters and clinical outcome is unclear.Methods Retrospective evaluation of irAEs on survival was performed across primary (N = 144) and secondary (N = 211) independent cohorts of patients with metastatic melanoma receiving single agent (pembrolizumab/nivolumab—sICB) or combination (nivolumab and ipilimumab—cICB) checkpoint blockade. RNA from pre-treatment and post-treatment CD8+ T cells was sequenced and differential gene expression according to irAE development assessed.Results 58.3% of patients developed early irAEs and this was associated with longer progression-free (PFS) and overall survival (OS) across both cohorts (log-rank test, OS: P < 0.0001). Median survival for patients without irAEs was 16.6 months (95% CI: 10.9–33.4) versus not-reached (P = 2.8 × 10−6). Pre-treatment monocyte and neutrophil counts, but not BMI, were additional predictors of clinical outcome. Differential expression of numerous gene pathway members was observed in CD8+ T cells according to irAE development, and patients not developing irAEs demonstrating upregulated CXCR1 pre- and post-treatment.Conclusions Early irAE development post-ICB is associated with favourable survival in MM. Development of irAEs is coupled to expression of numerous gene pathways, suggesting irAE development in-part reflects baseline immune activation.Subject terms: Immunotherapy, Melanoma 相似文献
79.
Kevin L. Greason Juan A. Crestanello Katherine S. King Gabor Bagameri Sertac M. Cicek John M. Stulak Richard C. Daly Joseph A. Dearani Hartzell V. Schaff 《The Journal of thoracic and cardiovascular surgery》2021,161(1):12-20.e2
BackgroundThere is controversy regarding the extent of aortic resection necessary in patients with aortopathy related to bicuspid aortic valve disease. To address this issue, we reviewed our experience in patients undergoing ascending aorta replacement during bicuspid aortic valve replacement.MethodsWe reviewed 702 patients who underwent ascending aorta replacement at the time of initial nonemergent native bicuspid aortic valve replacement at our institution between January 2000 and June 2017. Treatment cohorts included an open hemiarch replacement group (n = 225; 32%) and a clamped ascending aorta replacement group (n = 477; 68%).ResultsMedian patient age was 60 years (interquartile range [IQR], 51-67 years), female sex was present in 113 patients (16%), ejection fraction was 62% (IQR, 56%-66%), and aortic arch diameter was 33 mm (IQR, 29-36 mm). Cardiopulmonary bypass time was longer in the hemiarch replacement group (188 minutes vs 97 minutes; P < .001). Procedure-related complications (36%) and mortality (<1%) were similar in the 2 groups; however, the hemiarch group had an increased odds of blood transfusion (odds ratio, 1.62; 95% confidence interval [CI], 1.15-2.28; P = .006). The median duration of follow-up was 6.0 years (95% CI, 5.3-6.8 years). Overall survival was 94 ± 1% at 5 years and 80 ± 2% at 10 years. Multivariable analysis demonstrated similar survival in the 2 groups (hazard ratio, 0.83; 95% CI, 0.51-1.33; P = .439). No repeat aortic arch operations were done for aortopathy over the duration of clinical follow-up.ConclusionsCompared with patients in the clamped ascending aorta replacement group, patients in the hemi-arch replacement group had longer cardiopulmonary bypass and aortic cross-clamp times, along with an increased risk of blood transfusion, but similar freedom from repeat aortic arch operation and survival. We identified no advantage of performing hemiarch replacement in the absence of aortic arch dilation. 相似文献