全文获取类型
收费全文 | 1178篇 |
免费 | 107篇 |
国内免费 | 8篇 |
专业分类
耳鼻咽喉 | 14篇 |
儿科学 | 55篇 |
妇产科学 | 24篇 |
基础医学 | 263篇 |
口腔科学 | 11篇 |
临床医学 | 117篇 |
内科学 | 270篇 |
皮肤病学 | 13篇 |
神经病学 | 129篇 |
特种医学 | 21篇 |
外科学 | 88篇 |
综合类 | 5篇 |
预防医学 | 113篇 |
眼科学 | 5篇 |
药学 | 97篇 |
中国医学 | 1篇 |
肿瘤学 | 67篇 |
出版年
2023年 | 15篇 |
2022年 | 24篇 |
2021年 | 43篇 |
2020年 | 22篇 |
2019年 | 42篇 |
2018年 | 42篇 |
2017年 | 29篇 |
2016年 | 39篇 |
2015年 | 46篇 |
2014年 | 50篇 |
2013年 | 60篇 |
2012年 | 121篇 |
2011年 | 113篇 |
2010年 | 51篇 |
2009年 | 32篇 |
2008年 | 66篇 |
2007年 | 78篇 |
2006年 | 81篇 |
2005年 | 56篇 |
2004年 | 65篇 |
2003年 | 58篇 |
2002年 | 48篇 |
2001年 | 7篇 |
2000年 | 3篇 |
1999年 | 6篇 |
1998年 | 10篇 |
1997年 | 7篇 |
1996年 | 10篇 |
1995年 | 7篇 |
1994年 | 8篇 |
1993年 | 3篇 |
1992年 | 4篇 |
1991年 | 4篇 |
1990年 | 4篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1982年 | 5篇 |
1981年 | 4篇 |
1980年 | 2篇 |
1974年 | 1篇 |
1965年 | 1篇 |
1964年 | 1篇 |
1963年 | 1篇 |
1962年 | 1篇 |
1961年 | 1篇 |
1960年 | 2篇 |
1959年 | 2篇 |
1955年 | 2篇 |
1938年 | 2篇 |
1927年 | 1篇 |
排序方式: 共有1293条查询结果,搜索用时 0 毫秒
41.
Estelle J.A. Suys Dallas B. Warren Anna C. Pham Cameron J. Nowell Andrew J. Clulow Hassan Benameur Christopher J.H. Porter Colin W. Pouton David K. Chalmers 《Journal of pharmaceutical sciences》2019,108(1):193-204
Polyethoxylated, nonionic surfactants are important constituents of many drug formulations, including lipid-based formulations. In an effort to better understand the behavior of formulation excipients at the molecular level, we have developed molecular dynamics (MD) models for the widely used surfactant Kolliphor EL (KOL), a triricinoleate ester of ethoxylated glycerol. In this work, we have developed models based on a single, representative molecular component modeled with 2 force field variations based on the GROMOS 53A6DBW and 2016H66 force field parameters for polyethoxylate chains. To compare the computational models to experimental measurements, we investigated the phase behavior of KOL using nephelometry, dynamic light scattering, cross-polarized microscopy, small-angle X-ray scattering, and cryogenic transmission electron microscopy. The potential for digestion of KOL was also evaluated using an in vitro digestion experiment. We found that the size and spherical morphology of the KOL colloids at low concentrations was reproduced by the MD models as well as the growing interactions between the aggregates to from rod-like structures at high concentrations. We believe that this model reproduces the phase behavior of KOL relevant to drug absorption and that it can be used in whole formulation simulations to accelerate the formulation development. 相似文献
42.
Rahma Mani Sabrina Belkacem Zohra Soua Sandra Chantot Guy Montantin Sylvie Tissier Bruno Copin Jihene Bouguila Nicolas Rive Le Gouard Lamia Boughamoura Salma Ben Ameur Mongia Hachicha Raoudha Boussoffara Khadija Boussetta Samia Hammouda Abir Bedoui Habib Besbes Seif Meddeb Karima Chraeit Monia Khlifa Estelle Escudier Serge Amselem Imed Mabrouk Marie Legendre 《Human mutation》2020,41(1):115-121
Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disease of motile cilia. Even though PCD is widely studied, North‐African patients have been rarely explored. In this study, we aim at confirming the clinical diagnosis and explore the genetic spectrum of PCD in a cohort of Tunisian patients. Forty clinically diagnosed patients with PCD belonging to 34 families were recruited from Tunisian pediatric departments. In each proband, targeted capture PCD panel sequencing of the 40 PCD genes was performed. PCD panel sequencing identified bi‐allelic mutations in 82% of the families in eight PCD genes. Remarkably, 23.5% of patients carried the same c.2190del CCDC39 mutation. Single nucleotide polymorphism profiling in six unrelated patients carrying this mutation has revealed a founder effect in North‐African patients. This mutation is estimated to date back at least 1,400–1,750 years ago. The identification of this major allele allowed us to suggest a cost‐effective genetic diagnostic strategy in North‐African patients with PCD. 相似文献
43.
44.
45.
46.
Site selection for fat autotransplantation: Some observations 总被引:4,自引:0,他引:4
The use of autologous fat for implantation has recently received renewed attention in the plastic surgery literature. Autologous fat reportedly has been used for the treatment of wrinkles and Romberg's disease, and for buttock and breast augmentation. While some measure of success has been achieved, many surgeons report that substantial resorption of fat tissue occurs at the site of implantation. There is lack of unanimity regarding the ideal site for extraction or injection in order to minimize fat resorption. Adipose tissue samples were taken from women undergoing surgical procedures on the abdomen, gluteal-femoral region, and breast. Facial adipose tissue samples from men and women were also analyzed. Adipocytes were isolated chemically and sized microscopically. Activity of the lipogenic enzyme adipose tissue lipoprotein lipase (ATLPL) was measured in frozen samples. Results suggest that femoral site samples are somewhat larger (NS) and have greater lipogenic activity (p<0.03) than other sites. In our study, small facial samples had very low or unmeasurable levels of ATLPL activity. Perhaps cell size and lipogenic activity should be considered when selecting tissues for autotransplantation. 相似文献
47.
Kamel?MohammediEmail author Louis?Potier Maud?Fran?ois Dured?Dardari Marilyne?Feron Estelle?Nobecourt-Dupuy Manuel?Dolz Roxane?Ducloux Abdelkader?Chibani Dominique-Fran?ois?Eveno Teresa?Crea Avila Ariane?Sultan Laurence?Baillet-Blanco Vincent?Rigalleau Gilberto?Velho Florence?Tubach Ronan?Roussel Jean-Claude?Dupré Dominique?Malgrange Michel?Marre 《Journal of foot and ankle research》2016,9(1):34
Background
Off-loading is essential for diabetic foot management, but remains understudied. The evaluation of Off-loading using a new removable oRTHOsis in DIABetic foot (ORTHODIAB) trial aims to evaluate the efficacy of a new removable device “Orthèse Diabète” in the healing of diabetic foot.Methods/design
ORTHODIAB is a French multi-centre randomized, open label trial, with a blinded end points evaluation by an adjudication committee according to the Prospective Randomized Open Blinded End-point. Main endpoints are adjudicated based on the analysis of diabetic foot photographs. Orthèse Diabète is a new removable off-loading orthosis (PROTEOR, France) allowing innovative functions including real-time evaluation of off-loading and estimation of patients’ adherence. Diabetic patients with neuropathic plantar ulcer or amputation wounds (toes or transmetatarsal) are assigned to one of 2 parallel-groups: Orthèse Diabète or control group (any removable device) according to a central computer-based randomization. Study visits are scheduled for 6 months (days D7 and D14, and months M1, M2, M3, and M6). The primary endpoint is the proportion of patients whose principal ulcer is healed at M3. Secondary endpoints are: the proportion of patients whose principal ulcer is healed at M1, M2 and M6; the proportion of patients whose initial ulcers are all healed at M1, M2, M3, and M6; principal ulcer area reduction; time-related ulcer-free survival; development of new ulcers; new lower-extremity amputation; infectious complications; off-loading adherence; and patient satisfaction. The study protocol was approved by the French National Agency for Medicines and Health Products Safety, and by the ethics committee of Saint-Louis Hospital (Paris). Comprehensive study information including a Patient Information Sheet has been provided to each patient who must give written informed consent before enrolment. Monitoring, data management, and statistical analyses are providing by UMANIS Life Science (Paris), independently to the sponsor. Since 27/10/2013, 13 centres have agreed to participate in this study, 117 participants were included, and 70 have achieved the study schedules. The study completion is expected for the end of 2016, and the main results will be published in 2017.Conclusion
ORTHODIAB trial evaluates an innovating removable off-loading device, seeking to improve diabetic foot healing (ClinicalTrials.gov identifier: NCT01956162).48.
A novel coumarin‐quinone derivative SV37 inhibits CDC25 phosphatases,impairs proliferation,and induces cell death 下载免费PDF全文
49.
Maxime Thoreau HweiXian Leong Penny KarWai Tan Fabienne Regnier Julia Miriam Weiss Bernett Lee Ludger Johannes Estelle Dransart Agnès Le Bon Jean-Pierre Abastado Eric Tartour Alain Trautmann Nadège Bercovici 《Oncotarget》2015,6(29):27832-27846
Most cancer immunotherapies under present investigation are based on the belief that cytotoxic T cells are the most important anti-tumoral immune cells, whereas intra-tumoral macrophages would rather play a pro-tumoral role. We have challenged this antagonistic point of view and searched for collaborative contributions by tumor-infiltrating T cells and macrophages, reminiscent of those observed in anti-infectious responses. We demonstrate that, in a model of therapeutic vaccination, cooperation between myeloid cells and T cells is indeed required for tumor rejection. Vaccination elicited an early rise of CD11b+ myeloid cells that preceded and conditioned the intra-tumoral accumulation of CD8+ T cells. Conversely, CD8+ T cells and IFNγ production activated myeloid cells were required for tumor regression. A 4-fold reduction of CD8+ T cell infiltrate in CXCR3KO mice did not prevent tumor regression, whereas a reduction of tumor-infiltrating myeloid cells significantly interfered with vaccine efficiency. We show that macrophages from regressing tumors can kill tumor cells in two ways: phagocytosis and TNFα release. Altogether, our data suggest new strategies to improve the efficiency of cancer immunotherapies, by promoting intra-tumoral cooperation between macrophages and T cells. 相似文献
50.
Géraldine Mitou Julie Frentzel Aurore Desquesnes Sophie Le Gonidec Talal AlSaati Isabelle Beau Laurence Lamant Fabienne Meggetto Estelle Espinos Patrice Codogno Pierre Brousset Sylvie Giuriato 《Oncotarget》2015,6(30):30149-30164
Anaplastic Lymphoma Kinase-positive Anaplastic Large Cell Lymphomas (ALK+ ALCL) occur predominantly in children and young adults. Their treatment, based on aggressive chemotherapy, is not optimal since ALCL patients can still expect a 30% 2-year relapse rate. Tumor relapses are very aggressive and their underlying mechanisms are unknown. Crizotinib is the most advanced ALK tyrosine kinase inhibitor and is already used in clinics to treat ALK-associated cancers. However, crizotinib escape mechanisms have emerged, thus preventing its use in frontline ALCL therapy. The process of autophagy has been proposed as the next target for elimination of the resistance to tyrosine kinase inhibitors. In this study, we investigated whether autophagy is activated in ALCL cells submitted to ALK inactivation (using crizotinib or ALK-targeting siRNA). Classical autophagy read-outs such as autophagosome visualization/quantification by electron microscopy and LC3-B marker turn-over assays were used to demonstrate autophagy induction and flux activation upon ALK inactivation. This was demonstrated to have a cytoprotective role on cell viability and clonogenic assays following combined ALK and autophagy inhibition. Altogether, our results suggest that co-treatment with crizotinib and chloroquine (two drugs already used in clinics) could be beneficial for ALK-positive ALCL patients. 相似文献