全文获取类型
收费全文 | 344篇 |
免费 | 34篇 |
国内免费 | 1篇 |
专业分类
儿科学 | 3篇 |
妇产科学 | 12篇 |
基础医学 | 56篇 |
口腔科学 | 1篇 |
临床医学 | 25篇 |
内科学 | 119篇 |
皮肤病学 | 10篇 |
神经病学 | 42篇 |
外科学 | 29篇 |
综合类 | 1篇 |
预防医学 | 31篇 |
眼科学 | 13篇 |
药学 | 14篇 |
中国医学 | 1篇 |
肿瘤学 | 22篇 |
出版年
2024年 | 1篇 |
2023年 | 5篇 |
2022年 | 14篇 |
2021年 | 29篇 |
2020年 | 19篇 |
2019年 | 18篇 |
2018年 | 18篇 |
2017年 | 10篇 |
2016年 | 17篇 |
2015年 | 16篇 |
2014年 | 17篇 |
2013年 | 27篇 |
2012年 | 30篇 |
2011年 | 32篇 |
2010年 | 8篇 |
2009年 | 11篇 |
2008年 | 29篇 |
2007年 | 23篇 |
2006年 | 26篇 |
2005年 | 13篇 |
2004年 | 5篇 |
2003年 | 3篇 |
2002年 | 2篇 |
2000年 | 1篇 |
1999年 | 2篇 |
1995年 | 1篇 |
1982年 | 1篇 |
1972年 | 1篇 |
排序方式: 共有379条查询结果,搜索用时 17 毫秒
21.
Iryna Mogilevkina Birgit Bdker Alexander Orda Jens Langhoff-Roos Gunilla Lindmark 《European journal of obstetrics, gynecology, and reproductive biology》2002,100(2):152-157
Objective: To identify health care issues important to reduce the perinatal mortality rate (PMR) in Ukraine. Study Design: Perinatal deaths in the Donetsk region (Ukraine) in 1997–1998 were compared with those in Denmark in 1996 by using the Nordic–Baltic classification for perinatal deaths. Clinical guidelines, use of technology and rates of interventions in the two regions were described. Results: A two-fold increase in PMR was found in Ukraine compared to Denmark, mainly explained by higher rates of antenatal deaths of growth restricted fetuses, intrapartum deaths, and neonatal deaths due to asphyxia. Vacuum extraction is rarely used in Ukraine. The clinical guidelines for care differ significantly between the two regions. Conclusion: Appropriate use of technology and implementation of evidence-based guidelines should be a matter of high priority in the Donetsk region, Ukraine. 相似文献
22.
23.
Daniel F. Gluzman Iryna V. Abramenko Liliya M. Sklyarenko Valentina A. Nadgornaya Michael P. Zavelevich Nadia I. Bilous Ludmila Yu Poludnenko 《Pediatric hematology and oncology》1999,16(4):355-360
During 1993-1997, 247 cases of childhood acute leukemia (AL) were analyzed among inhabitants of the city of Kiev and Kiev region, excluding the most contaminated areas belonging to the strict control zone. The criteria of an FAB classification supplemented by immunophenotyping data were applied. The AL pattern was shown to be quite typical except for several peculiar features characteristic of this regional group of patients, especially the absence of age peaks in children with acute myelogenous leukemias (AML), increased frequency of the T1 variant in T-cell acute lymphoblastic leukemia (ALL), and higher levels of M4 and M5 variants in AML. A typical variant of M5a-AML with minimal signs of differentiation was found. 相似文献
24.
Ammad Ahmad Farooqi Sundas Fayyaz Iryna Shatynska‐Mytsyk Zeeshan Javed Saima Jabeen Ilhan Yaylim Maria Luisa Gasparri Pierluigi Benedetti Panici 《Chemical biology & drug design》2016,87(3):321-334
Overwhelmingly increasing advancements in miRNA biology have opened new avenues for pharmaceutical companies to initiate studies on designing effective, safe, and therapeutically active candidates using miRNA mimetics and miRNA inhibitors. In accordance with this approach, development of miravirsen and SPC3649, an LNA‐based (locked nucleic acid) antisense molecule against miR‐122, to treat hepatitis C has sparked interest in identifying most efficient microRNAs for journey from bench‐top toward pharmaceutical industry and breakthroughs in delivery technology will pave the way to ‘final frontier’. MRX34, a liposome‐formulated mimic of miR‐34 for treatment of metastatic cancer with liver involvement and unresectable primary liver cancer, has also entered in clinical trial. There is a successive increase in the research work related to miR‐34 biology and miRNA regulation of modulators of intracellular signaling cascades. We partition this review into how miR‐34a is regulated by different proteins and how Wnt‐ and TGF‐induced intracellular signaling cascades are modulated by miR‐34a. In this review, we bring to limelight how miR‐34a regulates its target genes to induce apoptosis and inhibit cell proliferation as evidenced by in vitro and in vivo analysis. We also discuss miR‐34 regulation of PDGFR and c‐MET and recent advancements in nanotechnologically delivered miR‐34a. Spotlight is also set on modulation of chemotherapeutic sensitivity by miR‐34a in cancer cells using reconstruction studies. Clinical trial of miR‐34 is indicative of its tremendous potential, and continuous cutting research will prove to be effective in efficiently translating laboratory findings into clinically effective therapeutics. 相似文献
25.
Shengqing Gu Stephanie Lheureux Azin Sayad Paulina Cybulska Liat Hogen Iryna Vyarvelska Dongsheng Tu Wendy R. Parulekar Matthew Nankivell Sean Kehoe Dennis S. Chi Douglas A. Levine Marcus Q. Bernardini Barry Rosen Amit Oza Myles Brown Benjamin G. Neel 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(25)
High-grade serous tubo-ovarian carcinoma (HGSC) is a major cause of cancer-related death. Treatment is not uniform, with some patients undergoing primary debulking surgery followed by chemotherapy (PDS) and others being treated directly with chemotherapy and only having surgery after three to four cycles (NACT). Which strategy is optimal remains controversial. We developed a mathematical framework that simulates hierarchical or stochastic models of tumor initiation and reproduces the clinical course of HGSC. After estimating parameter values, we infer that most patients harbor chemoresistant HGSC cells at diagnosis and that, if the tumor burden is not too large and complete debulking can be achieved, PDS is superior to NACT due to better depletion of resistant cells. We further predict that earlier diagnosis of primary HGSC, followed by complete debulking, could improve survival, but its benefit in relapsed patients is likely to be limited. These predictions are supported by primary clinical data from multiple cohorts. Our results have clear implications for these key issues in HGSC management.Ovarian cancer is the eighth most common cancer and cancer death in women worldwide (1). High-grade serous tubo-ovarian cancer (HGSC) constitutes ∼70% of all ovarian malignancies and has the worst prognosis (2). Current treatment of most patients with HGSC consists of cytoreductive surgery and combination chemotherapy with platinum-containing DNA–cross-linking drugs and taxane-based microtubule-stabilizing agents (2). Although treatment significantly improves survival, most women relapse with chemotherapy-refractory disease and eventually succumb (3). Multiple mechanisms of chemoresistance have been documented (4, 5), including reduced intracellular drug accumulation (6), detoxification by increased levels of glutathione (7), altered DNA damage repair (8, 9), dysfunctional apoptotic pathways (10, 11), and hyperactivation of various cell signaling pathways (12–14). These mechanistic studies are consistent with recent genomic analyses that reveal marked clonal evolution of HGSC during therapy (15). Other evidence, however, supports a hierarchical organization of HGSC, featuring intrinsically chemoresistant “cancer stem cells” (CSCs) that can escape initial treatment and seed recurrence (16–18).Although there is uniform agreement that HGSC patients should receive surgery and chemotherapy, the optimal order and timing of these modalities remain controversial. Two main options exist: primary debulking surgery with adjuvant chemotherapy (PDS), or neoadjuvant chemotherapy, followed by interval debulking surgery (NACT) (19–24). In either case, the surgical standard of care is to seek maximal cytoreduction, with the objective being to leave no visible residual disease. However, the precise definition of such “optimal debulking” can vary among different centers, surgeons, and reports (19, 21, 24, 25).Several studies have found similar outcomes after PDS or NACT, including two highly influential randomized trials (EORTC and CHORUS) carried out across multiple countries (22, 23, 26–28). In both trials, however, the question of potential bias in patient recruitment has been raised, favoring potentially those with more extensive disease, who are less likely benefit from “upfront” surgery (23, 28). Consistent with this interpretation, overall survival in these trials was significantly shorter than that seen in other HGSC cohorts (19, 24, 29, 30). Closer examination of these reports reveals additional factors that might have influenced their conclusions. The EORTC study had inconsistencies in optimal debulking rates between participating centers, with the PDS-associated complete debulking data highly influenced by the results from a single institution (23). The CHORUS study involved 76 clinical sites, and there were substantial differences in surgery execution and chemotherapy drug selection/dosage between them (28).At Princess Margaret Cancer Center, retrospective data showed that PDS patients with no visible disease postresection survived substantially longer (7-y survival, >60%) than those receiving NACT (7-y survival, ∼10%). Furthermore, although residual tumor postresection is a critical determinant of survival, its influence on the PDS group was far more dramatic than on NACT group (24). Of course, this report suffers from deficiencies common to all retrospective analyses, including lack of randomization to account for tumor burden at diagnosis and other factors; indeed, the NACT group in this study did have more extensive disease.Another controversy in HGSC management focuses on the potential benefit of earlier diagnosis. Earlier diagnosis of primary HGSC is generally assumed to enhance patient survival and quality of life (3). Intuitively, one might predict that the same reasoning would apply to recurrent disease; however, survival is similar in relapsed patients treated earlier, based on increasing serum CA125 levels, than in those treated only when physical symptoms of recurrence appear (31). Conceivably, the lead time between CA125 rise and clinical recurrence is too short for earlier chemotherapy to be beneficial; if so, then patient survival might be extended by more sensitive methods, such as testing for circulating tumor DNA (ctDNA) (32, 33).To address these issues, we developed a mathematical framework that models the dynamics of HGSC progression, response to surgery and chemotherapy, and recurrence. Our results, generated over a wide range of parameters and accounting for hierarchical and stochastic models of tumor initiation, argue that PDS is superior to NACT when complete debulking is feasible and suggest that, with currently available therapies, the benefits of earlier detection are intrinsically restricted to primary HGSC. 相似文献
26.
27.
Edmond Bendaly Anand A. Dalal Kenneth Culver Philip Galebach Iryna Bocharova Rebekah Foster Medha Sasane Alexander R. Macalalad Annie Guérin 《Advances in therapy》2017,34(7):1673-1685
Introduction
Crizotinib is recommended as first-line therapy for ALK-positive non-small cell lung cancer (NSCLC), but within a year of treatment initiation many patients develop resistance. With the recent approval of second-generation ALK inhibitors, this study assessed how physicians monitor for and diagnose progression and how they alter treatment following progression on crizotinib.Methods
A panel of oncologists from the United States were surveyed regarding their monitoring practices and criteria for diagnosing progression on crizotinib. The physicians also retrospectively provided data (March–June 2016) from the medical charts of their adult patients with locally advanced or metastatic ALK-positive NSCLC who progressed on crizotinib after the approval (April 2014) of the first second-generation ALK inhibitor, ceritinib.Results
A total of 28 physicians responded to the survey. Data was abstracted on 74 patients. In the physician survey, most physicians (71%) reported monitoring for radiographic progression every 3–4 months. When new lesions were detected, physician response varied. Following a symptomatic isolated lesion, most physicians (75%) would add local therapy and resume crizotinib. Following multiple symptomatic lesions, 96% and 64% of physicians would switch to a new therapy depending on whether the lesions were extracranial or isolated to the brain, respectively. For the patient cohort, physician-defined progression on crizotinib was diagnosed after a median of 10 months, and within 30 days of diagnosis, 86% of patients discontinued crizotinib. Among all patients who discontinued crizotinib, 77% switched to ceritinib, 14% to chemotherapy, and 1% to alectinib. The remaining 7% did not receive additional systemic antineoplastic therapy.Conclusion
The findings from this physician survey and retrospective chart review study suggest that physician response to the development of new lesions in crizotinib-treated ALK-positive NSCLC patients varies with location and extent of the lesions. Once patients were considered to have progressed, most of them were immediately switched to ceritinib.Funding
Novartis Pharmaceuticals Corporation.28.
GSK3ß‐dependent dysregulation of neurodevelopment in SPG11‐patient induced pluripotent stem cell model 下载免费PDF全文
Himanshu K. Mishra PhD Iryna Prots PhD Steven Havlicek PhD Zacharias Kohl MD Francesc Perez‐Branguli PhD Tom Boerstler BSc Lukas Anneser MSc Georgia Minakaki MSc Holger Wend Martin Hampl MSc Marina Leone PhD Martina Brückner Jochen Klucken MD Andre Reis MD Leah Boyer PhD Gerhard Schuierer MD Jürgen Behrens PhD Angelika Lampert MD Felix B. Engel PhD Fred H. Gage PhD Jürgen Winkler MD Beate Winner MD 《Annals of neurology》2016,79(5):826-840
29.
Power calculations and placebo effect for future clinical trials in progressive supranuclear palsy 下载免费PDF全文
30.