全文获取类型
收费全文 | 1008篇 |
免费 | 42篇 |
国内免费 | 5篇 |
专业分类
耳鼻咽喉 | 6篇 |
儿科学 | 22篇 |
妇产科学 | 14篇 |
基础医学 | 126篇 |
口腔科学 | 1篇 |
临床医学 | 67篇 |
内科学 | 242篇 |
皮肤病学 | 11篇 |
神经病学 | 127篇 |
特种医学 | 19篇 |
外科学 | 212篇 |
综合类 | 6篇 |
一般理论 | 2篇 |
预防医学 | 49篇 |
眼科学 | 28篇 |
药学 | 74篇 |
中国医学 | 3篇 |
肿瘤学 | 46篇 |
出版年
2023年 | 11篇 |
2022年 | 19篇 |
2021年 | 25篇 |
2020年 | 6篇 |
2019年 | 23篇 |
2018年 | 24篇 |
2017年 | 14篇 |
2016年 | 28篇 |
2015年 | 27篇 |
2014年 | 38篇 |
2013年 | 34篇 |
2012年 | 59篇 |
2011年 | 85篇 |
2010年 | 52篇 |
2009年 | 24篇 |
2008年 | 56篇 |
2007年 | 59篇 |
2006年 | 60篇 |
2005年 | 37篇 |
2004年 | 51篇 |
2003年 | 50篇 |
2002年 | 44篇 |
2001年 | 12篇 |
2000年 | 5篇 |
1999年 | 5篇 |
1998年 | 11篇 |
1997年 | 5篇 |
1996年 | 8篇 |
1992年 | 7篇 |
1991年 | 6篇 |
1990年 | 6篇 |
1989年 | 6篇 |
1988年 | 6篇 |
1985年 | 6篇 |
1983年 | 7篇 |
1979年 | 9篇 |
1978年 | 6篇 |
1977年 | 4篇 |
1974年 | 7篇 |
1973年 | 5篇 |
1972年 | 9篇 |
1971年 | 10篇 |
1970年 | 4篇 |
1969年 | 5篇 |
1968年 | 4篇 |
1967年 | 4篇 |
1965年 | 4篇 |
1964年 | 4篇 |
1962年 | 4篇 |
1957年 | 7篇 |
排序方式: 共有1055条查询结果,搜索用时 15 毫秒
81.
Laura Giardino Silvia Armelloni Alessandro Corbelli Deborah Mattinzoli Cristina Zennaro Dominique Guerrot Fabien Tourrel Masami Ikehata Min Li Silvia Berra Michele Carraro Piergiorgio Messa Maria P. Rastaldi 《Journal of the American Society of Nephrology : JASN》2009,20(9):1929-1940
Podocytes possess the complete machinery for glutamatergic signaling, raising the possibility that neuron-like signaling contributes to glomerular function. To test this, we studied mice and cells lacking Rab3A, a small GTPase that regulates glutamate exocytosis. In addition, we blocked the glutamate ionotropic N-methyl-d-aspartate receptor (NMDAR) with specific antagonists. In mice, the absence of Rab3A and blockade of NMDAR both associated with an increased urinary albumin/creatinine ratio. In humans, NMDAR blockade, obtained by addition of ketamine to general anesthesia, also had an albuminuric effect. In vitro, Rab3A-null podocytes displayed a dysregulated release of glutamate with higher rates of spontaneous exocytosis, explained by a reduction in Rab3A effectors resulting in freedom of vesicles from the actin cytoskeleton. In addition, NMDAR antagonism led to profound cytoskeletal remodeling and redistribution of nephrin in cultured podocytes; the addition of the agonist NMDA reversed these changes. In summary, these results suggest that glutamatergic signaling driven by podocytes contributes to the integrity of the glomerular filtration barrier and that derangements in this signaling may lead to proteinuric renal diseases.It is widely recognized that most glomerular diseases are characterized by defects of the filtration barrier, where podocytes play a central role. Mutations of single podocyte proteins have been found at the basis of human nephrotic syndromes,1 and podocyte deletion of the same molecules causes heavy proteinuria in experimental models.2–8Podocytes are highly ramified cells: From the cell body depart a number of primary processes, further originating secondary foot processes. Starting from these features, it has been demonstrated that podocytes share numerous similarities with neurons: They both are terminally differentiated cells, have a common cytoskeletal organization, and have a common machinery of process formation.9 Furthermore, a number of expression-restricted proteins, such as nephrin,2 Neph1 and Neph2,10 GLEPP1,11 CAT3 and EAAT2,12 synaptopodin,13 drebrin,14 and Sam68-like-MP2,15 specifically belong to the podocyte and the neuron.Our group has contributed to this line of research, initially by describing in podocytes the presence of Rab3A, a small GTPase that is mostly enriched in synaptic vesicles because it tightly modulates highly regulated exocytosis by acting through a number of effector molecules, including rabphilin-3a and Synapsin-I.16 After finding that in podocytes, as it occurs in neurons, Rab3A associates to glutamate-containing vesicles along cell processes, we discovered that podocytes are equipped with a complete neuron-like glutamatergic signaling system.17 We described that podocytes possess functional synaptic-like microvesicles and renal glomeruli express cognate glutamate transporters and receptors. These properties strengthened the analogies between podocytes and neurons and offered a rational interpretation to the biochemical similarity of foot process and synaptic adhesion complexes17; however, the role played by glutamate signaling in podocytes remained unanswered, and nothing was known about its relevance to podocyte and glomerular homeostasis. To get more details on the requirement of this neuron-like system of signaling by podocytes, we first conducted a preliminary analysis on its temporal appearance during podocyte differentiation. Then we studied conditions in which it was altered, on the vesicle and on the receptor side. The vesicular component was analyzed by studying the consequences of the absence of Rab3A. On the receptor side, we antagonized the ionotropic N-methyl-d-aspartate receptor (NMDAR), that we found present in human and rodent glomeruli, as well as in podocyte cell cultures.17 Both Rab3A and NMDAR1 glomerular synthesis were also confirmed by in situ hybridization (Supplemental Figure 1) and by microarray expression data.17 相似文献
82.
Lochner K Gaemlich A Südel KM Venzke K Moll I Knott A Stäb F Wenck H Döring O Böttger M Gallinat S 《Biogerontology》2007,8(3):269-282
Extracellular matrix (ECM) organization is a complex process that requires the coordinated efforts of many molecules. For
the regulation of collagen fiber diameter, the proteoglycan decorin appears to be of major relevance. To investigate the role
of decorin in the process of (photo-)aging in more detail, full-thickness punch biopsies were isolated from human buttock
skin. Single exposure with two minimal erythemal doses of solar simulated irradiation caused down-regulation of decorin mRNA
in young (n = 5) and old subjects (n = 5) after 24 h. Interestingly, decorin mRNA was elevated with age. To test the hypothesis that a decreased collagen-to-decorin-ratio
impairs collagen structure we also investigated collagens I and III gene expression. Both were down-regulated with increasing
age and after single UV-irradiation. As determined by laser capture microdissection-quantitative real time-Polymerase chain
reaction (n = 11), decorin is mostly present in the reticular dermis while being absent from the papillary dermis. Minor expression was
also observed in the epidermis. However, in contrast to full-thickness skin biopsies age-dependent changes in collagens I,
III, and decorin expression could not be observed with this methodology indicating technical limitations. Together with our
finding that collagens I and III mRNA are similarly expressed in the reticular and papillary dermis and are down-regulated
by UV, our studies support the idea of a major role of decorin in ECM organization. Altered expression of decorin mRNA in
the different dermal strata and a decrease in the collagen-to-decorin ratio inflicted by both age and ultraviolet irradiation
possibly affect collagen bundle diameter and subsequently the mechanical properties of human skin. 相似文献
83.
le Roux R Niehaus DJ Koen L Seller C Lochner C Emsley RA 《Transcultural psychiatry》2007,44(2):292-299
Although traditional initiation forms a pivotal part of Xhosa culture, it may be a stressful life event for the individual. In this study, 75 Xhosa males diagnosed with schizophrenia were interviewed to examine their perceptions of the role of initiation in the onset and course of their illness. In all, eight patients (10.7%) perceived the initiation rites as a stressful event that had triggered the onset of a psychotic episode, and six (8%) felt it precipitated a relapse. Our findings suggest that initiation rituals may be perceived as a stressful life event influencing the onset and course of schizophrenia. This underlines the importance of understanding the cultural background of patients. 相似文献
84.
Bertocchini A Falappa P Accinni A Devito R Inserra A 《The Annals of thoracic surgery》2007,84(6):2091-2093
We report on an infant presenting with a chondroid hamartoma managed with a combined conservative surgical treatment and radiofrequency thermoablation. 相似文献
85.
Midrio P Stefanutti G Mussap M D'Antona D Zolpi E Gamba P 《Journal of pediatric surgery》2007,42(5):777-782
Background/Purpose
Amniotic fluid of fetuses with gastroschisis (GS) contains inflammatory mediators, gastrointestinal, and urinary waste products. Dilution and removal of such harmful substances have been advocated to prevent damage to the herniated intestine. We evaluated the effectiveness of serial amnioexchange procedures in 8 consecutive fetuses with GS.Methods
Amnioexchange was performed bimonthly during the third trimester. Amniotic fluid collected before each procedure was tested for pH, osmolarity, urea, creatinine, cystatin-C, proteins, albumin, bilirubin, biliary salts, pancreatic amylase, serum amyloid A, C-reactive protein, alanine transaminase (ALT), alcaline phosphatase (ALP), gamma-glutamyl transpetidase (γGT), tumor necrosis factor α, interleukin 2, interleukin 6, epidermal growth factor, transforming growth factor β, and myeloperoxidase.Results
A total of 25 samples (median, 3 per fetus) were examined. Biochemical or inflammatory markers did not correlate with gestational age, nor was any trend observed in values from individual patients during the course of amnioexchange treatment. There was no correlation between biochemical or inflammatory markers and clinical outcome, including time to full enteral feeding.Conclusions
Serial amnioexchanges did not modify the biochemical or inflammatory status of amniotic fluid nor appeared to prevent injury to the herniated gut. Because repeated amnioexchanges may carry some risks, their use in fetuses with GS is not recommended outside the setting of a prospective randomized trial. 相似文献86.
Ethnopharmacological relevance
Diabetes mellitus is rampantly increasing and the need for therapeutics is crucial. In recognition of this, untested antidiabetic agents are flooding the market. Diavite™ which is a product consisting solely of the dried and ground pods of Prosopis glandulosa (Torr.) [Fabaceae] is currently marketed as a food supplement with glucose stabilizing properties. However, these are anecdotal claims lacking scientific evidence. The aim of this study was to determine the efficacy of Prosopis glandulosa as an antidiabetic agent.Materials and methods
Male Wistar rats were rendered (a) type 1 diabetic after an intraperitoneal injection of STZ (40 mg/kg) and (b) insulin resistant after a 16-week high caloric diet (DIO). Zucker fa/fa ZDF rats were used in a pilot study. Half of each group of animals was placed on Prosopis glandulosa treatment (100 mg/kg/day) for 8 weeks and the remaining animals served as age-matched controls. At the time of sacrifice, blood was collected for glucose and insulin level determination, the pancreata of the STZ rats were harvested for histological analysis and cardiomyocytes prepared from the DIO and Zucker fa/fa hearts for determination of insulin sensitivity.Results
Type 1 diabetic model: Prosopis glandulosa treatment resulted in significant increased insulin levels (p < 0.001), which was accompanied by a significant decrease in blood glucose levels (p < 0.05). Additionally, Prosopis glandulosa treatment resulted in increased small β-cells (p < 0.001) in the pancreata. The body weight of the STZ animals decreased significantly after STZ injection, with Prosopis glandulosa treatment partially preventing this. Zucker fa/fa rats: Prosopis glandulosa treatment significantly reduced fasting glucose levels (p < 0.01) and improved IPGTT, when comparing treated to untreated animals. DIO insulin resistant model: Prosopis glandulosa treatment resulted in an increased basal (p < 0.01) and insulin-stimulated (p < 0.05) glucose uptake by cardiomyocytes prepared from this group.Conclusions
The present study showed that Prosopis glandulosa treatment moderately lowers glucose levels in different animal models of diabetes, stimulates insulin secretion, leads to the formation of small β-cells and improves insulin sensitivity of isolated cardiomyocytes. 相似文献87.
Berruti A Generali D Kaufmann M Puztai L Curigliano G Aglietta M Gianni L Miller WR Untch M Sotiriou C Daidone M Conte P Kennedy D Damia G Petronini P Di Cosimo S Bruzzi P Dowsett M Desmedt C Mansel RE Olivetti L Tondini C Sapino A Fenaroli P Tortora G Thorne H Bertolini F Ferrozzi F Danova M Tagliabue E de Azambuja E Makris A Tampellini M Dontu G Van't Veer L Harris AL Fox SB Dogliotti L Bottini A 《Journal of the National Cancer Institute. Monographs》2011,2011(43):147-151
A panel of international breast cancer experts formulated a declaration of consensus regarding many key issues in the use of primary systemic therapy (PST) either in clinical routine or research practice. The attainment of pathological complete response (pCR), defined as no residual invasive tumor in the surgical specimens both in breast and in axillary nodes, is one of the main goals of PST, and pCR can be used as the primary objective in prospective clinical trials. However, pCR is not a reliable endpoint with all treatment approaches, and alternatives such as Ki67 index of the residual invasive disease or after 2 weeks of PST are also potential endpoints. PST has several advantages: breast conservation and the unique opportunity to obtain information on the interaction between treatment and tumor biology. Changes in tumor biology after PST are an early phenomenon; so, an additional core biopsy performed after 14 days from treatment start should be considered in clinical trials. 相似文献
88.
Nardone R Ausserer H Bratti A Covi M Lochner P Marth R Florio I Tezzon F 《Headache》2008,48(4):578-585
BACKGROUND: Head pain arises within the trigeminal nociceptive system. Current theories propose that the trigeminal system is intimately involved in the pathogenesis of migraine. Short-latency responses can be recorded in sternocleidomastoid muscles after stimulation of the trigeminal nerve (trigemino-cervical reflex). This brainstem reflex could be a suitable method to evaluate the trigeminal system in migraine and CH. OBJECTIVE: The aim of the present study was to further elucidate the pathophysiology of migraine and cluster headache (CH) with special reference to the involvement of the central trigeminal system in the different forms of primary headache. METHODS: The trigemino-cervical reflex was investigated in 15 healthy subjects, in 15 patients having migraine with aura, in 15 patients with migraine without aura, and in 10 patients with CH. RESULTS: Significant abnormalities were observed in a great number of patients with both types of migraine and CH during the headache attacks, but only in migraine patients during the interictal period. The alterations are bilateral in migraine, unilateral in CH. CONCLUSIONS: Our results further support the relevance of brainstem mechanisms in the pathogenesis of migraine rather than of CH. These data, taken together with that from experimental head pain and functional imaging studies, demonstrate that primary headache syndromes may be distinguished on a functional basis by areas of activation specific to the clinical syndrome. 相似文献
89.
Fogazzi GB Edefonti A Garigali G Giani M Zolin A Raimondi S Mihatsch MJ Messa P 《Pediatric nephrology (Berlin, Germany)》2008,23(7):1093-1100
The evaluation of urinary erythrocyte morphology (UEM) has been proposed for patients with isolated microscopic haematuria (IMH) to early orientate the diagnosis towards a glomerular or a nonglomerular disease. However, to date, the role of this test in patients with IMH has very rarely been investigated. Sixteen patients (ten children, six adults) with persistent IMH classified as glomerular on the basis of repeated UEM evaluations (55 urine samples, two to eight per patient) were submitted to renal biopsy. This showed a glomerular disease in 14/16 patients (87.5%) (nine thin basement membrane disease; three Alport syndrome; two other), whereas in two patients, no abnormalities were found. Of four microscopic criteria investigated to define a IMH as glomerular, >80% dysmorphic erythrocytes were not found in any sample, >or=40% dysmorphic erythrocytes alone were seen in seven samples (12.7%), >or=5% acanthocytes alone in 15 samples (27.3%) and erythrocytic casts in six samples (10.9%). There was >or=40% dysmorphic erythrocytes associated with >or=5% acanthocytes in 25 samples (45.5%). Sensitivity and positive predictive values in diagnosing a glomerular haematuria were 59.2% and 90.6%, respectively, for >or=40% dysmorphic erythrocytes, 69.4% and 85% for >or=5% acanthocytes/G1 cells and 12.2% and 100% for erythrocytic casts. Our findings demonstrate that the evaluation of UEM is useful to identify patients with an IMH of glomerular origin. 相似文献
90.
Neri Piergiorgio Herbort Carl P. Hedayatfar Alireza Tugal-Tutkun Ilknur Cimino Luca Urzua Cristhian A. Papasavvas Ioannis Takeuchi Masuru Lages Vania 《International ophthalmology》2022,42(1):1-6
International Ophthalmology - 相似文献