全文获取类型
收费全文 | 520篇 |
免费 | 31篇 |
国内免费 | 1篇 |
专业分类
儿科学 | 9篇 |
妇产科学 | 1篇 |
基础医学 | 30篇 |
口腔科学 | 5篇 |
临床医学 | 19篇 |
内科学 | 113篇 |
皮肤病学 | 1篇 |
神经病学 | 12篇 |
特种医学 | 9篇 |
外科学 | 173篇 |
综合类 | 5篇 |
一般理论 | 1篇 |
预防医学 | 10篇 |
眼科学 | 6篇 |
药学 | 63篇 |
中国医学 | 2篇 |
肿瘤学 | 93篇 |
出版年
2024年 | 1篇 |
2023年 | 6篇 |
2022年 | 8篇 |
2021年 | 39篇 |
2020年 | 22篇 |
2019年 | 16篇 |
2018年 | 24篇 |
2017年 | 18篇 |
2016年 | 16篇 |
2015年 | 15篇 |
2014年 | 36篇 |
2013年 | 48篇 |
2012年 | 56篇 |
2011年 | 44篇 |
2010年 | 26篇 |
2009年 | 14篇 |
2008年 | 33篇 |
2007年 | 20篇 |
2006年 | 24篇 |
2005年 | 11篇 |
2004年 | 8篇 |
2003年 | 13篇 |
2002年 | 6篇 |
2001年 | 3篇 |
2000年 | 5篇 |
1999年 | 7篇 |
1998年 | 7篇 |
1997年 | 3篇 |
1996年 | 3篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 4篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1903年 | 1篇 |
1902年 | 1篇 |
排序方式: 共有552条查询结果,搜索用时 31 毫秒
41.
A comprehensive view of sex-specific issues related to cardiovascular disease 总被引:7,自引:3,他引:7 下载免费PDF全文
Louise Pilote Kaberi Dasgupta Veena Guru Karin H. Humphries Jennifer McGrath Colleen Norris Doreen Rabi Johanne Tremblay Arsham Alamian Tracie Barnett Jafna Cox William Amin Ghali Sherry Grace Pavel Hamet Teresa Ho Susan Kirkland Marie Lambert Danielle Libersan Jennifer O'Loughlin Gilles Paradis Milan Petrovich Vicky Tagalakis 《Canadian Medical Association journal》2007,176(6):S1-S44
Cardiovascular disease (CVD) is the leading cause of mortality in women. In fact, CVD is responsible for a third of all deaths of women worldwide and half of all deaths of women over 50 years of age in developing countries. The prevalence of CVD risk factor precursors is increasing in children. Retrospective analyses suggest that there are some clinically relevant differences between women and men in terms of prevalence, presentation, management and outcomes of the disease, but little is known about why CVD affects women and men differently. For instance, women with diabetes have a significantly higher CVD mortality rate than men with diabetes. Similarly, women with atrial fibrillation are at greater risk of stroke than men with atrial fibrillation. Historically, women have been underrepresented in clinical trials. The lack of good trial evidence concerning sex-specific outcomes has led to assumptions about CVD treatment in women, which in turn may have resulted in inadequate diagnoses and suboptimal management, greatly affecting outcomes. This knowledge gap may also explain why cardiovascular health in women is not improving as fast as that of men. Over the last decades, mortality rates in men have steadily declined, while those in women remained stable. It is also becoming increasingly evident that gender differences in cultural, behavioural, psychosocial and socioeconomic status are responsible, to various degrees, for the observed differences between women and men. However, the interaction between sex-and gender-related factors and CVD outcomes in women remains largely unknown. 相似文献
42.
The objective of this study is to determine the effect of various neutral liposomes on corneal and conjunctival permeability of didanosine (ddI), an antiviral drug. Multi-lamellar vesicles (MLVs), large unilamellar vesicles (LUVs), and sonicated multi-lamellar vesicles (SMLVs) encapsulating ddI (with trace quantities of 3HddI) were prepared using distearoyl phosphatidylcholine (DSPC), a neutral lipid. The liposomes contained 14C-cholesteryl oleate as a lipid tracer. Liposome formulations containing free and encapsulated drug (f + e) and those containing only encapsulated drug (e) of an equal quantity were compared with free drug in this study. The permeability studies were conducted in the mucosal to serosal direction across excised rabbit cornea and conjunctiva. The percent encapsulation of ddI in MLVs, LUVs, and SMLVs was 25.66 0.30, 26.56 0.57, and 19.41 0.30, respectively. The mean particle size of MLVs, LUVs, and SMLVs containingfree and encapsulated drug was 3058, 774, and 270 nm, respectively. With all liposome formulations tested, the percent uptake of lipid by tissues was higher compared to ddI uptake. While ddI permeated across the tissues, the lipid tracer did not permeate in detectable quantities.The SMLV(e) formulation was better than the SMLV(f + e) formulation with respect to initial flux and tissue uptake in both tissues and permeability across conjunctiva. In general, the permeability coefficient, initial flux, and tissue levels of ddI at the end of the transport study were lower in the presence of all liposome formulations compared to free drug. Thus, neutral liposomal encapsulation is not a suitable approach to enhance the corneal or conjunctival transport or uptake of ddI. 相似文献
43.
Mammalian target of rapamycin (mTOR) inhibitors have emerged as a major addition to the therapeutic armamentarium for renal
cell carcinoma. Temsirolimus extended survival when employed as frontline therapy for poor-risk advanced renal cell carcinoma.
Everolimus has demonstrated improved progression-free survival for all risk groups of RCC in the salvage setting following
other anti-angiogenic agents. Preliminary data indicates that baseline activation of the mTOR signaling pathway and increased
FDG-PET uptake as well as early pharmacodynamic modulations of the mTOR pathway and down-modulation of FDG-PET uptake may
predict for the activity of mTOR inhibitors. Ongoing trials are attempting to validate these data with everolimus therapy
for metastatic RCC and may enable the goal of personalized therapy. 相似文献
44.
Experimental infection of golden hamsters with Leishmania donovani caused significant alterations in the hepatic microsomal mixed function oxidase system. Gross examination of liver indicated hepatomegaly. Microsomal protein contents were only marginally elevated. Cytochrome P-450 as well as haem contents were significantly decreased and it directly correlated with the degree of infection. Cytochrome b5 exhibited elevation at lower degrees of infection which came down to control levels at the peak infection. Concomitant suppression was also noticed in cytochrome P-450 dependent monooxygenase activities, viz. aniline hydroxylase, benzo[a]pyrene hydroxylase and aminopyrine N-demethylase. No significant change was observed in NADH-cytochrome b5 reductase and NADPH-cytochrome c reductase. The results indicate suppression of hepatic microsomal MFO activities during visceral leishmaniasis. 相似文献
45.
Sean?A.?Fletcher Sabrina?S.?Harmouch Marieke?J.?Krimphove Alexander?P.?Cole Sebastian?Berg Philipp?Gild Mark?A.?Preston Guru?P.?Sonpavde Adam?S.?Kibel Maxine?Sun Toni?K.?Choueiri Quoc-Dien?TrinhEmail authorView authors OrcID profile 《World journal of urology》2018,36(11):1767-1774
Introduction
Muscle-invasive bladder cancer (MIBC) is an aggressive disease for which treatment strategies are continuously evolving. We characterized trends in treatment modalities for MIBC from 2004 to 2013 (the “pre-immunotherapy era”) and identified predictors of receiving the current standard of care treatment: neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC).Methods
We used the National Cancer Database to identify individuals diagnosed with clinically localized MIBC from 2004 to 2013. We calculated the yearly prevalence of NAC followed by RC, RC as first treatment, trimodal therapy, chemotherapy and/or radiation alone, and no treatment. We then identified factors associated with receiving NAC prior to RC.Results
There was a notable increase in the use of NAC followed by RC over the study period, from 3.68% in 2004 to 14.83% in 2013 (P?<?0.001). Factors associated with decreased odds of receiving this regimen included being older, Black, uninsured, less educated, and more burdened by comorbidities. Rates of trimodal therapy and chemotherapy and/or radiation alone remained relatively constant (approximately 5 and 17%, respectively). There was a consistent decline in the proportion of patients who did not receive any treatment, down to 34.20% in 2013.Conclusion
Trends in localized MIBC treatment have evolved substantially since the early 2000s, and certain patient characteristics are associated with lower odds of receiving the current standard of care. This serves as a foundation from which to judge the impact of the upcoming immunotherapy era on the treatment landscape for this disease.46.
Matthew D. Galsky Huan Wang Noah M. Hahn Przemyslaw Twardowski Sumanta K. Pal Costantine Albany Mark T. Fleming Alexander Starodub Ralph J. Hauke Menggang Yu Qianqian Zhao Guru Sonpavde Michael J. Donovan Vaibhav G. Patel John P. Sfakianos Josep Domingo-Domenech William K. Oh Nicholas Akers Andrew V. Uzilov 《European urology》2018,73(5):751-759
Background
Chemotherapy may exert immunomodulatory effects, thereby combining favorably with the immune checkpoint blockade. The pharmacodynamic effects of such combinations, and potential predictive biomarkers, remain unexplored.Objective
To determine the safety, efficacy, and immunomodulatory effects of gemcitabine and cisplatin (GC) plus ipilimumab and explore the impact of somatic DNA damage response gene alterations on antitumor activity.Design, setting, and participants
Multicenter single arm phase 2 study enrolling 36 chemotherapy-naïve patients with metastatic urothelial cancer. Peripheral blood flow cytometry was performed serially on all patients and whole exome sequencing of archival tumor tissue was performed on 28/36 patients.Intervention
Two cycles of GC followed by four cycles of GC plus ipilimumab.Outcome measurements and statistical analysis
The primary endpoint was 1-yr overall survival (OS). Secondary endpoints included safety, objective response rate, and progression-free survival.Results and limitations
Grade ≥3 adverse events occurred in 81% of patients, the majority of which were hematologic. The objective response rate was 69% and 1-yr OS was 61% (lower bound 90% confidence interval: 51%). On exploratory analysis, there were no significant changes in the composition and frequency of circulating immune cells after GC alone. However, there was a significant expansion of circulating CD4 cells with the addition of ipilimumab which correlated with improved survival. The response rate was significantly higher in patients with deleterious somatic DNA damage response mutations (sensitivity = 47.6%, specificity = 100%, positive predictive value = 100%, and negative predictive value = 38.9%). Limitations are related to the sample size and single-arm design.Conclusions
GC + ipilimumab did not achieve the primary endpoint of a lower bound of the 90% confidence interval for 1-yr OS of >60%. However, within the context of a small single-arm trial, the results may inform current approaches combining chemotherapy plus immunotherapy from the standpoint of feasibility, appropriate cytotoxic backbones, and potential predictive biomarkers. Trial registration: ClinicalTrials.gov NCT01524991.Patient summary
Combining chemotherapy and immune checkpoint blockade in patients with metastatic urothelial cancer is feasible. Further studies are needed to refine optimal combinations and evaluate tests that might identify patients most likely to benefit. 相似文献47.
C11orf95‐RELA fusion present in a primary intracranial extra‐axial ependymoma: Report of a case with literature review 下载免费PDF全文
Aruna Nambirajan Prit Benny Malgulwar Mehar C. Sharma Anutosh Singh Pankaj Pathak Guru Dutta Satyarthee Ajay Garg 《Neuropathology》2016,36(5):490-495
Ependymomas are gliomas that recapitulate the ependymal cells microscopically and ultrastructurally. They commonly occur along the ventricular surfaces and central canal of the brain and spinal cord. Intracranial extra‐axial ependymoma (IEAE) is a rare entity and is commonly misdiagnosed clinically and radiologically as a meningioma. The histogenesis of such IEAEs is obscure. A novel recurrent oncogenic fusion involving the C11orf95 and RELA genes was recently described in supratentorial ependymomas. A 9‐year‐old girl presented with a dural based parafalcine mass that, in addition to exhibiting classical immunohistochemical features of an ependymoma, also demonstrated C11orf95‐RELA fusion, characteristic of supratentorial ependymomas. We suggest that IEAEs share their histogenesis with their intra‐axial counterparts, arising either from dural extension of subcortical, subependymal rests or directly from ectopic dural rests. 相似文献
48.
Ahmed A. Hussein Paul R. May Zhe Jing Youssef E. Ahmed Carl J. Wijburg Abdulla Erdem Canda Prokar Dasgupta Mohammad Shamim Khan Mani Menon James O. Peabody Abolfazl Hosseini John Kelly Alexandre Mottrie Jihad Kaouk Ashok Hemal Peter Wiklund Khurshid A. Guru 《The Journal of urology》2018,199(5):1302-1311
49.
Guru PK Phillips S Ball MM Das A Singh S 《The Indian journal of chest diseases & allied sciences》2005,47(3):209-211
Signet ring cell carcinoma is a unique mucin secreting adenocarcinoma. It generally arises from stomach, colon, rectum or breast and rarely from lung. Pleural membrane involvement is common in lung cancer manifesting as pleural effusion. Rarely, it may encase the whole lung without effusion mimicking mesothelioma and is termed as "pseudomesothelioma". A 35-year-old male presented with a pleural mass encasing the whole of the right lung without any pleural effusion and investigations revealed it to be primary signet ring cell adenocarcinoma of the lung. 相似文献
50.
Toti US Guru BR Hali M McPharlin CM Wykes SM Panyam J Whittum-Hudson JA 《Biomaterials》2011,32(27):6606-6613
Chlamydia trachomatis and Chlamydia pneumoniae are intracellular bacterial pathogens that have been shown to cause, or are strongly associated with, diverse chronic diseases. Persistent infections by both organisms are refractory to antibiotic therapy. The lack of therapeutic efficacy results from the attenuated metabolic rate of persistently infecting chlamydiae in combination with the modest intracellular drug concentrations achievable by normal delivery of antibiotics to the inclusions within which chlamydiae reside in the host cell cytoplasm. In this research, we evaluated whether nanoparticles formulated using the biodegradable poly(d-L-lactide-co-glycolide) (PLGA) polymer can enhance the delivery of antibiotics to the chlamydial inclusion complexes. We initially studied the trafficking of PLGA nanoparticles in Chlamydia-infected cells. We then evaluated nanoparticles for the delivery of antibiotics to the inclusions. Intracellular trafficking studies show that PLGA nanoparticles efficiently concentrate in inclusions in both acutely and persistently infected cells. Further, encapsulation of rifampin and azithromycin antibiotics in PLGA nanoparticles enhanced the effectiveness of the antibiotics in reducing microbial burden. Combination of rifampin and azithromycin was more effective than the individual drugs. Overall, our studies show that PLGA nanoparticles can be effective carriers for targeted delivery of antibiotics to intracellular chlamydial infections. 相似文献