全文获取类型
收费全文 | 1689篇 |
免费 | 117篇 |
国内免费 | 9篇 |
专业分类
耳鼻咽喉 | 10篇 |
儿科学 | 24篇 |
妇产科学 | 49篇 |
基础医学 | 216篇 |
口腔科学 | 9篇 |
临床医学 | 158篇 |
内科学 | 392篇 |
皮肤病学 | 18篇 |
神经病学 | 308篇 |
特种医学 | 25篇 |
外科学 | 169篇 |
综合类 | 5篇 |
一般理论 | 1篇 |
预防医学 | 114篇 |
眼科学 | 34篇 |
药学 | 80篇 |
中国医学 | 3篇 |
肿瘤学 | 200篇 |
出版年
2022年 | 14篇 |
2021年 | 45篇 |
2020年 | 13篇 |
2019年 | 23篇 |
2018年 | 41篇 |
2017年 | 31篇 |
2016年 | 29篇 |
2015年 | 37篇 |
2014年 | 53篇 |
2013年 | 57篇 |
2012年 | 83篇 |
2011年 | 112篇 |
2010年 | 51篇 |
2009年 | 66篇 |
2008年 | 89篇 |
2007年 | 92篇 |
2006年 | 90篇 |
2005年 | 70篇 |
2004年 | 57篇 |
2003年 | 77篇 |
2002年 | 71篇 |
2001年 | 36篇 |
2000年 | 22篇 |
1999年 | 34篇 |
1998年 | 15篇 |
1997年 | 15篇 |
1996年 | 13篇 |
1994年 | 15篇 |
1993年 | 18篇 |
1992年 | 23篇 |
1991年 | 26篇 |
1990年 | 29篇 |
1989年 | 21篇 |
1988年 | 22篇 |
1987年 | 28篇 |
1986年 | 24篇 |
1985年 | 18篇 |
1984年 | 13篇 |
1983年 | 18篇 |
1981年 | 12篇 |
1979年 | 17篇 |
1978年 | 12篇 |
1976年 | 17篇 |
1975年 | 11篇 |
1974年 | 13篇 |
1973年 | 11篇 |
1972年 | 12篇 |
1971年 | 11篇 |
1970年 | 13篇 |
1969年 | 16篇 |
排序方式: 共有1815条查询结果,搜索用时 15 毫秒
61.
62.
Gender influence on schizophrenia‐relevant abnormalities in a cuprizone demyelination model
下载免费PDF全文
![点击此处可从《Glia》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The aim of this study was to determine whether early demyelination can impact behavior in young adulthood. For this purpose, albino Wistar rats of either sex were exposed to cuprizone (CPZ) in two different intoxication protocols: one group was intoxicated before weaning (CPZ‐BW), from postnatal day 7 (P7) to P21, through maternal milk, whereas the other group was intoxicated after weaning (CPZ‐AW), from P21 to P35. After treatment, rats were returned to a normal diet until P90 when behavioral studies were performed. Both treatments produced marked demyelination in the corpus callosum and retraction of cortical myelin fibers. The subsequent normal diet allowed for effective remyelination at P90. Interestingly, CPZ‐AW correlated with significant behavioral and neurochemical changes in a gender‐dependent manner. CPZ‐AW treatment altered both the number of social activities and the latency to the first social interaction in males, while also highly compromising recognition‐related activities. In addition, only P90 males treated AW showed a hyperdopaminergic striatum, confirmed by an increase in tyrosine hydroxylase expression and in dopamine levels. Our results suggest that the timing of demyelination significantly influences the development of altered behavior, particularly in adult males. GLIA 2014;62:1629–1644 相似文献
63.
An Vo Bruce T Volpe Chris C Tang Wynne K Schiffer Czeslawa Kowal Patricio T Huerta Aziz M Ulu? Stephen L Dewey David Eidelberg Betty Diamond 《Journal of cerebral blood flow and metabolism》2014,34(8):1315-1320
Systemic lupus erythematosus (SLE) is characterized by multiorgan inflammation, neuropsychiatric disorders (NPSLE), and anti-nuclear antibodies. We previously identified a subset of anti-DNA antibodies (DNRAb) cross-reactive with the N-methyl-D-aspartate receptor, present in 30% to 40% of patients, able to enhance excitatory post-synaptic potentials and trigger neuronal apoptosis. DNRAb+ mice exhibit memory impairment or altered fear response, depending on whether the antibody penetrates the hippocampus or amygdala. Here, we used 18F-fluorodeoxyglucose (FDG) microPET to plot changes in brain metabolism after regional blood–brain barrier (BBB) breach. In DNRAb+ mice, metabolism declined at the site of BBB breach in the first 2 weeks and increased over the next 2 weeks. In contrast, DNRAb− mice exhibited metabolic increases in these regions over the 4 weeks after the insult. Memory impairment was present in DNRAb+ animals with hippocampal BBB breach and altered fear conditioning in DNRAb+ mice with amygdala BBB breach. In DNRAb+ mice, we observed an inverse relationship between neuron number and regional metabolism, while a positive correlation was observed in DNRAb− mice. These findings suggest that local metabolic alterations in this model take place through different mechanisms with distinct time courses, with important implications for the interpretation of imaging data in SLE subjects. 相似文献
64.
65.
Miriam Araña Juan J. Gavira Estefanía Peña Arantxa González Gloria Abizanda Myriam Cilla Marta M. Pérez Edurne Albiasu Natalia Aguado Mayte Casado Begoña López Susana González Mario Soriano Cristina Moreno Juana Merino José M. García-Verdugo Javier Díez Manuel Doblaré Beatriz Pelacho Felipe Prosper 《Biomaterials》2014
Although transplantation of adipose-derived stem cells (ADSC) in chronic myocardial infarction (MI) models is associated with functional improvement, its therapeutic value is limited due to poor long-term cell engraftment and survival. Thus, the objective of this study was to examine whether transplantation of collagen patches seeded with ADSC could enhance cell engraftment and improve cardiac function in models of chronic MI. With that purpose, chronically infarcted Sprague–Dawley rats (n = 58) were divided into four groups and transplanted with media, collagen scaffold (CS), rat ADSC, or CS seeded with rat ADSC (CS-rADSC). Cell engraftment, histological changes, and cardiac function were assessed 4 months after transplantation. In addition, Göttingen minipigs (n = 18) were subjected to MI and then transplanted 2 months later with CS or CS seeded with autologous minipig ADSC (CS-pADSC). Functional and histological assessments were performed 3 months post-transplantation. Transplantation of CS-rADSC was associated with increased cell engraftment, significant improvement in cardiac function, myocardial remodeling, and revascularization. Moreover, transplantation of CS-pADSC in the pre-clinical swine model improved cardiac function and was associated with decreased fibrosis and increased vasculogenesis. In summary, transplantation of CS-ADSC resulted in enhanced cell engraftment and was associated with a significant improvement in cardiac function and myocardial remodeling. 相似文献
66.
Antonio-Santos Anabel Pérez-Campos Eduardo Hernández-Cruz Pedro Antonio Solórzano-Mata Carlos Narváez-Morales Juana Torres-Aguilar Honorio Villegas-Sepúlveda Nicolás Aguilar-Ruiz Sergio Roberto 《Human immunology》2014
Platelets functions in hemostasis have been widely studied. Currently, growing evidence shows that platelets have also a role in the immune innate response. Recently, protein expression of Toll-like receptors (TLR’s) 2, 4, 7, 8, and 9, and the presence of TLRs 1 and 6 mRNA in human platelets was described. Up to now the functionality of TLR-2, 4 and 9 in human platelets has been demonstrated. Due to the relevance of TLRs functions to PAMPS (pathogen-associated molecular patterns) recognizing, we evaluated the presence of TLR3 in human platelets founding low percentages of platelets expressing surface or intracellular TLR3 protein. The activation with thrombin induced an increase in the percentage of platelets expressing surface TLR3 and higher levels of TLR3 expression in the whole population. Human platelets responded to poly I:C by increasing [Ca2+]i, the percentages of cells expressing TLR4 and CD62P, and by releasing CXCL4 and IL-1β in comparison to unstimulated platelets. These results demonstrate that human platelets express TLR3 and are capable of responding to poly I:C, suggesting that these cells might influence the immune innate response when detecting viral dsRNA. 相似文献
67.
68.
Juana Angel Odile Colard Franoise Chevy Catherine Fournier 《Arthritis \u0026amp; Rheumatology》1993,36(2):158-167
Objective. Interleukin-1 (IL-1), an important mediator contributing to joint destruction in rheumatoid arthritis, is known to stimulate the release of arachidonic acid (AA) and prostaglandin E2 (PGE2) from adherent synoviocytes. To study the intracellular pathways involved in these functions, we stimulated cultures of human synovial cells with recombinant IL-1β. Methods. AA liberation was measured after labeling synovial cells with 3H-AA, and PGE2 levels were determined by high performance liquid chromatography or radioimmunoassay. Identification of 3H-AA-labeled phospholipids was performed by thin layer chromatography. Cell-associated phospholipase A2 (PLA2) enzymatic activity was determined by an assay with cell-free systems and exogenous substrates. Results. Stimulation of synovial cells with recombinant IL-1β induced a decrease in phosphatidylcholine (PC), phosphatidylinositol (PI), and phosphatidylethanolamine (PE), and a marked increase in cell-associated PLA2 activity as compared with controls. In the presence of either quinacrine, an inhibitor of PLA2 pathway activation, or neomycin, which binds to PI mono- and biphosphate thus blocking their degradation by phospholipases, AA and PGE2 secretion were reduced in a dose-dependent manner. Kinetic studies revealed that quinacrine had little blocking activity on the IL-1-mediated AA release after 1 hour of stimulation but completely abolished it after 5 or 8 hours. In contrast, neomycin exerted a partial but significant inhibitory effect from the first hour of stimulation onward. Addition of quinacrine was also demonstrated to abolish the IL-1-induced hydrolysis of PC and PE but not PI, indicating that PC and PE are the preferred substrates for PLA2 enzymatic activity in human synovial cells. Conclusion. Our findings strongly suggest that AA and PGE2 production by IL-1-triggered synoviocytes are largely dependent upon PLA2-mediated hydrolysis of PC and PE and to a lesser extent upon the earlier degradation of PI. 相似文献
69.
Lue Ping Zhao Terry P. Lybrand Peter B. Gilbert Thomas R. Hawn Joshua T. Schiffer Leonidas Stamatatos Thomas H. Payne Lindsay N. Carpp Daniel E. Geraghty Keith R. Jerome 《Viruses》2022,14(1)
The emergence and establishment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of interest (VOIs) and variants of concern (VOCs) highlight the importance of genomic surveillance. We propose a statistical learning strategy (SLS) for identifying and spatiotemporally tracking potentially relevant Spike protein mutations. We analyzed 167,893 Spike protein sequences from coronavirus disease 2019 (COVID-19) cases in the United States (excluding 21,391 sequences from VOI/VOC strains) deposited at GISAID from 19 January 2020 to 15 March 2021. Alignment against the reference Spike protein sequence led to the identification of viral residue variants (VRVs), i.e., residues harboring a substitution compared to the reference strain. Next, generalized additive models were applied to model VRV temporal dynamics and to identify VRVs with significant and substantial dynamics (false discovery rate q-value < 0.01; maximum VRV proportion >10% on at least one day). Unsupervised learning was then applied to hierarchically organize VRVs by spatiotemporal patterns and identify VRV-haplotypes. Finally, homology modeling was performed to gain insight into the potential impact of VRVs on Spike protein structure. We identified 90 VRVs, 71 of which had not previously been observed in a VOI/VOC, and 35 of which have emerged recently and are durably present. Our analysis identified 17 VRVs ~91 days earlier than their first corresponding VOI/VOC publication. Unsupervised learning revealed eight VRV-haplotypes of four VRVs or more, suggesting two emerging strains (B1.1.222 and B.1.234). Structural modeling supported a potential functional impact of the D1118H and L452R mutations. The SLS approach equally monitors all Spike residues over time, independently of existing phylogenic classifications, and is complementary to existing genomic surveillance methods. 相似文献
70.
Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study 总被引:50,自引:45,他引:50
下载免费PDF全文
![点击此处可从《Blood》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Talpaz M Silver RT Druker BJ Goldman JM Gambacorti-Passerini C Guilhot F Schiffer CA Fischer T Deininger MW Lennard AL Hochhaus A Ottmann OG Gratwohl A Baccarani M Stone R Tura S Mahon FX Fernandes-Reese S Gathmann I Capdeville R Kantarjian HM Sawyers CL 《Blood》2002,99(6):1928-1937
Chronic myelogenous leukemia (CML) is caused by expression of the BCR-ABL tyrosine kinase oncogene, the product of the t(9;22) Philadelphia translocation. Patients with CML in accelerated phase have rapidly progressive disease and are characteristically unresponsive to existing therapies. Imatinib (formerly STI571) is a rationally developed, orally administered inhibitor of the Bcr-Abl kinase. A total of 235 CML patients were enrolled in this study, of whom 181 had a confirmed diagnosis of accelerated phase. Patients were treated with imatinib at 400 or 600 mg/d and were evaluated for hematologic and cytogenetic response, time to progression, survival, and toxicity. Imatinib induced hematologic response in 82% of patients and sustained hematologic responses lasting at least 4 weeks in 69% (complete in 34%). The rate of major cytogenetic response was 24% (complete in 17%). Estimated 12-month progression-free and overall survival rates were 59% and 74%, respectively. Nonhematologic toxicity was usually mild or moderate, and hematologic toxicity was manageable. In comparison to 400 mg, imatinib doses of 600 mg/d led to more cytogenetic responses (28% compared to 16%), longer duration of response (79% compared to 57% at 12 months), time to disease progression (67% compared to 44% at 12 months), and overall survival (78% compared to 65% at 12 months), with no clinically relevant increase in toxicity. Orally administered imatinib is an effective and well-tolerated treatment for patients with CML in accelerated phase. A daily dose of 600 mg is more effective than 400 mg, with similar toxicity. 相似文献