全文获取类型
收费全文 | 318篇 |
免费 | 13篇 |
国内免费 | 26篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 14篇 |
妇产科学 | 1篇 |
基础医学 | 43篇 |
口腔科学 | 5篇 |
临床医学 | 45篇 |
内科学 | 60篇 |
皮肤病学 | 4篇 |
神经病学 | 52篇 |
特种医学 | 58篇 |
外科学 | 8篇 |
综合类 | 5篇 |
预防医学 | 2篇 |
眼科学 | 4篇 |
药学 | 50篇 |
中国医学 | 2篇 |
肿瘤学 | 3篇 |
出版年
2023年 | 1篇 |
2022年 | 1篇 |
2021年 | 5篇 |
2020年 | 1篇 |
2019年 | 1篇 |
2018年 | 4篇 |
2017年 | 3篇 |
2016年 | 4篇 |
2015年 | 6篇 |
2014年 | 4篇 |
2013年 | 5篇 |
2012年 | 10篇 |
2011年 | 13篇 |
2010年 | 5篇 |
2009年 | 13篇 |
2008年 | 15篇 |
2007年 | 30篇 |
2006年 | 8篇 |
2005年 | 7篇 |
2004年 | 6篇 |
2003年 | 6篇 |
2002年 | 5篇 |
2001年 | 8篇 |
2000年 | 4篇 |
1999年 | 7篇 |
1998年 | 17篇 |
1997年 | 18篇 |
1996年 | 13篇 |
1995年 | 12篇 |
1994年 | 14篇 |
1993年 | 15篇 |
1992年 | 4篇 |
1991年 | 8篇 |
1990年 | 2篇 |
1989年 | 8篇 |
1988年 | 12篇 |
1987年 | 5篇 |
1986年 | 7篇 |
1985年 | 9篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 5篇 |
1981年 | 2篇 |
1980年 | 5篇 |
1979年 | 1篇 |
1978年 | 8篇 |
1977年 | 5篇 |
1976年 | 6篇 |
1975年 | 3篇 |
1939年 | 1篇 |
排序方式: 共有357条查询结果,搜索用时 15 毫秒
1.
Geraldo F. Busatto Lyn S. Pilowsky Durval C. Costa John Mertehs Dirk Terriere Peter J. Ell Rachel Mulligan Michael J. Travis Josée E. Leysen Dominic Lui Sveto Gacinovic Wendy Waddington Anne Lingford-Hughes Robert W. Kerwin 《European journal of nuclear medicine and molecular imaging》1997,24(2):119-124
The mapping of 5-HT2 receptors in the brain using functional imaging techniques has been limited by a relative lack of selective radioligands.
Iodine-123 labelled 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide (123I-5-I-R91150 or123I-R93274) is a new ligand for single-photon emission tomography (SPET), with high affinity and selectivity for 5-HT2A receptors. This study reports on preliminary123I-5-I-R91150 SPET, wholebody and blood distribution findings in five healthy human volunteers. Maximal brain uptake was approximately
2% of total body counts at 180 min post injection (p.i.). Dynamic SPET sequences were acquired with the brain-dedicated, single-slice
multi-detector system SEM-810 over 200 min p.i. Early peak uptake (at 5 min p.i.) was seen in the cerebellum, a region free
from 5HT2A receptors. In contrast, radioligand binding in the frontal cortex increased steadily over time, up to a peak at approximately
100–120 min p.i. Frontal cortex-cerebellum activity ratios reached values of 1.4, and remained stable from approximately 100
min p.i. onwards. Multi-slice SPET sequences showed a pattern of regional variation of binding compatible with the autoradiographic
data on the distribution of 5-HT2A receptors in (cerebral cortex>striatum>cerebellum). These findings suggest that123I-5-I-R91150 may be used for the imaging of 5-HT2A receptors in the living human brain with SPET. 相似文献
2.
3.
4.
Direct evidence for the involvement of carbohydrate sequences in human sperm-zona pellucida binding 总被引:2,自引:0,他引:2
Several lines of evidence indicate that mammalian fertilization is
initiated via a binding process that is dependent upon the recognition of
oligosaccharide sequences associated with zona pellucida (ZP)
glycoproteins. Here, specific chemical and enzymatic methods were employed
to modify human ZP and to test their effects on sperm binding in the
hemizona assay system (HZA). Periodate oxidation of human ZP under very
mild conditions (10 min, 0 degrees C, 1 mM sodium m- periodate) that
attacks only terminal sialic acid resulted in a 30% loss of human sperm
binding in the HZA [hemizona index (HZI) = 70.2 +/- 10.9, n = 22; P <
0.05]. Periodate oxidation under mild conditions (1 h, 23 degrees C, 10 mM
sodium m-periodate) caused a 40% decrease in binding (HZI = 60.8 +/- 10.3;
n = 24; P< 0.01). Treatment of human ZP with neuraminidase caused a
substantial increase in sperm binding to human ZP (HZI = 297 +/- 45, n =
22; P < 0.01). These findings indicate that there are sialic acid
dependent binding sites coexisting with binding sites that are obscured by
sialic acid. To determine the periodate sensitivity of these obscured
sites, hemizona were first digested with neuraminidase and subsequently
subjected to mild periodate oxidation. The combined enzymatic and chemical
treatments caused a 79% decrease in sperm binding compared to control
hemizona (HZI = 20.7 +/- 4.4, n = 16; P < 0.001). Human sperm-ZP
interaction was also increased by digestion of human ZP with
endo-beta-galactosidase (HZI = 710 +/- 232, n = 14; P < 0.01),
indicating that potential binding sites for spermatozoa are also obscured
by lactosaminoglycan sequences. These studies support a definitive role for
the involvement of ZP-associated glycans in the binding of human
spermatozoa to oocytes.
相似文献
5.
6.
Jessica L. Ruiz Joshua D. Hutcheson Luis Cardoso Amirala Bakhshian Nik Alexandra Condado de Abreu Tan Pham Fabrizio Buffolo Sara Busatto Stefania Federici Andrea Ridolfi Masanori Aikawa Sergio Bertazzo Paolo Bergese Sheldon Weinbaum Elena Aikawa 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(14)
Vascular calcification predicts atherosclerotic plaque rupture and cardiovascular events. Retrospective studies of women taking bisphosphonates (BiPs), a proposed therapy for vascular calcification, showed that BiPs paradoxically increased morbidity in patients with prior acute cardiovascular events but decreased mortality in event-free patients. Calcifying extracellular vesicles (EVs), released by cells within atherosclerotic plaques, aggregate and nucleate calcification. We hypothesized that BiPs block EV aggregation and modify existing mineral growth, potentially altering microcalcification morphology and the risk of plaque rupture. Three-dimensional (3D) collagen hydrogels incubated with calcifying EVs were used to mimic fibrous cap calcification in vitro, while an ApoE−/− mouse was used as a model of atherosclerosis in vivo. EV aggregation and formation of stress-inducing microcalcifications was imaged via scanning electron microscopy (SEM) and atomic force microscopy (AFM). In both models, BiP (ibandronate) treatment resulted in time-dependent changes in microcalcification size and mineral morphology, dependent on whether BiP treatment was initiated before or after the expected onset of microcalcification formation. Following BiP treatment at any time, microcalcifications formed in vitro were predicted to have an associated threefold decrease in fibrous cap tensile stress compared to untreated controls, estimated using finite element analysis (FEA). These findings support our hypothesis that BiPs alter EV-driven calcification. The study also confirmed that our 3D hydrogel is a viable platform to study EV-mediated mineral nucleation and evaluate potential therapies for cardiovascular calcification.Atherosclerotic plaque rupture is the leading cause of myocardial infarction and stroke (1, 2). Studies assessing the correlation between calcium scores and cardiovascular events have demonstrated a predictive power that is superior to and independent from that of lipid scores (3, 4). Additionally, clinical imaging studies have revealed that the risk of plaque rupture is further heightened by the presence of small, “spotty” calcifications, or microcalcifications (5, 6), and cardiovascular risk is inversely correlated with the size of calcific deposits, quantified as a calcium density score (7). Indeed, computational modeling has demonstrated that, while large calcifications can reinforce the fibrous cap (8), microcalcifications (typically 5 to 15 μm in diameter) uniquely mediate an increase in mechanical stress of the relatively soft, collagen-rich fibrous cap (9–12).Histologic studies have revealed the presence of cell-derived vesicles within calcifying atherosclerotic lesions (13–16). The inflammatory environment of the atherosclerotic lesion can induce vascular smooth muscle cells (vSMCs) to take on an osteochondrogenic phenotype and release calcifying extracellular vesicles (EVs) (17–19). Macrophages have also been shown to release procalcifying vesicles (20, 21). Thus, just as bone formation is hypothesized to be an active, cell-driven process (22, 23), mediated by calcifying matrix vesicles, atheroma-associated calcification may similarly be initiated by the production and aggregation of calcifying EVs (11, 20, 24–28).One proposed strategy for halting pathologic calcification has been the use of bisphosphonates (BiPs). BiPs are analogs of pyrophosphate (29), a naturally occurring compound derived in vivo from adenosine triphosphate (ATP) (30). Pyrophosphate binds to calcium phosphate and inhibits calcification via physicochemical mechanisms, namely, by blocking calcium and phosphate ions from forming crystals, preventing crystal aggregation, and preventing mineral transformation from amorphous calcium phosphate to hydroxyapatite (29). BiPs were identified as pyrophosphate analogs that, unlike pyrophosphate itself, resist enzymatic hydrolysis. A second, distinct property of BiPs is the ability to inhibit bone resorption via biological activity directed against osteoclasts following osteoclast endocytosis of the BiP molecule adsorbed to the surface of bone (29, 31). First-generation, or nonnitrogen-containing BiPs, are incorporated into nonhydrolyzable ATP analogs, and induce osteoclast apoptosis by limiting ATP-dependent enzymes. In contrast, nitrogen-containing BiPs inhibit farnesyl pyrophosphate synthetase and thereby induce osteoclast apoptosis (31).In vivo animal investigations have been performed to explore the potential for BiPs to inhibit cardiovascular calcification. Studies of first-generation BiPs revealed that the doses required to inhibit cardiovascular calcification also critically compromised normal bone mineralization (29, 32). However, newer, nitrogen-containing BiPs effectively arrested cardiovascular calcification in animal models at doses that did not compromise bone formation (32). Further, while it has been proposed that BiP treatment modifies cardiovascular calcification via its impact on bone-regulated circulating calcium and phosphate levels, a study in uremic rats demonstrated that BiP treatment inhibited medial aortic calcification with no significant change in plasma calcium and phosphate levels (33). The same study demonstrated that BiP treatment inhibited calcification of explanted rat aortas, indicating that BiPs can act directly on vascular tissue, independent of bone metabolism (33).Retrospective clinical data examining the effect of BiP therapy on cardiovascular calcification has demonstrated conflicting findings and intriguing paradoxes. In women with chronic kidney disease, BiP therapy decreased the mortality rate for patients without a prior history of cardiovascular disease (34), but for those patients with a history of prior cardiovascular events, BiP therapy was associated with an increased mortality rate (35). In another study, BiP therapy correlated with a lower rate of cardiovascular calcification in older patients (>65 y), but a greater rate in younger patients (<65 y) (36). These clinical findings motivated our study, in which we sought to further understand how BiP therapy impacts cardiovascular outcomes. Given that cardiovascular calcification, and especially the presence of microcalcification, is a strong and independent risk factor for adverse cardiac events, and BiPs are prescribed to modulate pathologies of mineralization, we hypothesize that BiPs modulate cardiovascular outcomes by altering the dynamics of cardiovascular calcification.EVs are smaller than the resolution limits of traditional microscopy techniques, hindering studies into the mechanisms of calcification nucleation and growth. We previously developed an in vitro collagen hydrogel platform that allowed the visualization of calcific mineral development mediated by EVs isolated from vSMCs (24). Using superresolution microscopy, confocal, and electron microscopy techniques, we showed that calcification requires the accumulation of EVs that aggregate and merge to build mineral. Collagen serves as a scaffold that promotes associations between EVs that spread into interfibrillar spaces. The resultant mineral that forms within the collagen hydrogel appears spectroscopically similar to microcalcifications in human tissues and allows the study of these structures on the time scale of 1 wk. In this study, we utilized this three-dimensional (3D) acellular platform to examine the direct effect of ibandronate, a nitrogen-containing BiP, on the EV-directed nucleation and growth of microcalcifications, a process that cannot be isolated from cellular and tissue-level mechanisms in a more complex, in vivo system. In parallel, we utilized a mouse model of atherosclerosis to assess the effect of ibandronate therapy on plaque-associated calcification, comparing mineral morphologies between the in vitro and in vivo samples. We hypothesize that BiPs block EV aggregation and modify existing mineral growth, potentially altering microcalcification morphology and the risk of plaque rupture. Understanding the EV-specific action of BiPs is imperative both to develop anticalcific therapeutics targeting EV mineralization and to understand one potential mechanism driving the cardiovascular impact of BiPs used in clinical settings. 相似文献
7.
8.
Increased plasma levels of soluble TNF receptors 1 and 2 in bipolar depression and impact of lithium treatment
下载免费PDF全文
![点击此处可从《Human psychopharmacology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
9.
Chi DX Yan GZ Wang WX Lin LM Zhang GF Shi Y 《Journal of medical engineering & technology》2013,37(5):233-237
Manometry of the alimentary tract is a valuable and widely used means to evaluate and diagnose the function of the alimentary tract. However, the measurement can be inconvenient due to the invasive method used, and the many factors affecting results. Research on colonic pressure data is even more insufficient. This paper deals with colonic pressure data via an improved method ensuring that pressure data of the whole colon is available. The data is analysed based on the learning vector quantization (LVQ) method. Testing results show that this method distinguishes the normal data and the abnormal data, consistently with the original diagnoses. This method can serve as an assistant diagnosis of colonic motility and contributes to further research on colonic motility based on pressure data. 相似文献
10.
Suen Paulo J. C. Doll Sarah Batistuzzo Marcelo C. Busatto Geraldo Razza Lais B. Padberg Frank Mezger Eva Bulubas Lucia Keeser Daniel Deng Zhi-De Brunoni Andre R. 《European archives of psychiatry and clinical neuroscience》2021,271(1):101-110
European Archives of Psychiatry and Clinical Neuroscience - Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation intervention investigated for the treatment of... 相似文献