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61.
Agnieszka Arthur Romana A Panagopoulos Lachlan Cooper Danijela Menicanin Ian H Parkinson John D Codrington Kate Vandyke Andrew CW Zannettino Simon A Koblar Natalie A Sims Koichi Matsuo Stan Gronthos 《Journal of bone and mineral research》2013,28(4):926-935
Previous reports have identified a role for the tyrosine kinase receptor EphB4 and its ligand, ephrinB2, as potential mediators of both bone formation by osteoblasts and bone resorption by osteoclasts. In the present study, we examined the role of EphB4 during bone repair after traumatic injury. We performed femoral fractures with internal fixation in transgenic mice that overexpress EphB4 under the collagen type 1 promoter (Col1‐EphB4) and investigated the bone repair process up to 12 weeks postfracture. The data indicated that Col1‐EphB4 mice exhibited stiffer and stronger bones after fracture compared with wild‐type mice. The fractured bones of Col1‐EphB4 transgenic mice displayed significantly greater tissue and bone volume 2 weeks postfracture compared with that of wild‐type mice. These findings correlated with increased chondrogenesis and mineral formation within the callus site at 2 weeks postfracture, as demonstrated by increased safranin O and von Kossa staining, respectively. Interestingly, Col1‐EphB4 mice were found to possess significantly greater numbers of clonogenic mesenchymal stromal progenitor cells (CFU‐F), with an increased capacity to form mineralized nodules in vitro under osteogenic conditions, when compared with those of the wild‐type control mice. Furthermore, Col1‐EphB4 mice had significantly lower numbers of TRAP‐positive multinucleated osteoclasts within the callus site. Taken together, these observations suggest that EphB4 promotes endochondral ossification while inhibiting osteoclast development during callus formation and may represent a novel drug target for the repair of fractured bones. © 2013 American Society for Bone and Mineral Research. 相似文献
62.
Yao Liu Jerome A. Staal Alison J. Canty Matthew T. K. Kirkcaldie Anna E. King Olivier Bibari Stan T. Mitew Tracey C. Dickson James C. Vickers 《The Journal of comparative neurology》2013,521(8):1817-1827
The neurofilament light (NFL) subunit is considered as an obligate subunit polymer for neuronal intermediate filaments comprising the neurofilament (NF) triplet proteins. We examined cytoskeletal protein levels in the cerebral cortex of NFL knockout (KO) mice at postnatal day 4 (P4), 5 months, and 12 months of age compared with age‐matched wild‐type (WT) mice of a similar genetic background (C57BL/6). The absence of NFL protein resulted in a significant reduction of phosphorylated and dephosphorylated NFs (NF‐P, NF‐DP), the medium NF subunit (NFM), and the intermediate filament α‐internexin (INT) at P4. At 5 months, NF‐DP, NFM, and INT remained significantly lower in knockouts. At 12 months, NF‐P was again significantly decreased, and INT significantly increased, in KOs compared with wild type. In addition, protein levels of class III neuron‐specific β‐tubulin and microtubule‐associated protein 2 were significantly increased in NFL KO mice at P4, 5 months, and 12 months, whereas β‐actin levels were significantly decreased at P4. Immunocytochemical studies demonstrated that NF‐DP accumulated abnormally in the perikarya of cortical neurons by 5 months of age in NFL KO mice. Neurons that lacked NF triplet proteins, such as calretinin‐immunolabeled nonpyramidal cells, showed no alterations in density or cytoarchitectural distribution in NFL KO mice at 5 months relative to WT mice, although calretinin protein levels were decreased significantly after 12 months in NFL KO mice. These findings suggest that a lack of NFL protein alters the expression of cytoskeletal proteins and disrupts other NF subunits, causing intracellular aggregation but not gross structural changes in cortical neurons or cytoarchitecture. The data also indicate that changes in expression of other cytoskeletal proteins may compensate for decreased NFs. J. Comp. Neurol. 521:1817–1827, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
63.
Fang Ding Limin Zheng Min Liu Rongfa Chen L. Stan Leung Tao Luo 《Journal of anesthesia》2016,30(4):684-690
Background
Exposure to volatile anesthetics has been reported to cause temporary or sustained impairments in learning and memory in pre-clinical studies. The selective antagonists of the histamine H3 receptors (H3R) are considered to be a promising group of novel therapeutic agents for the treatment of cognitive disorders. The aim of this study was to evaluate the effect of H3R antagonist ciproxifan on isoflurane-induced deficits in an object recognition task.Methods
Adult C57BL/6 J mice were exposed to isoflurane (1.3 %) or vehicle gas for 2 h. The object recognition tests were carried at 24 h or 7 days after exposure to anesthesia to exploit the tendency of mice to prefer exploring novel objects in an environment when a familiar object is also present. During the training phase, two identical objects were placed in two defined sites of the chamber. During the test phase, performed 1 or 24 h after the training phase, one of the objects was replaced by a new object with a different shape. The time spent exploring each object was recorded.Results
A robust deficit in object recognition memory occurred 1 day after exposure to isoflurane anesthesia. Isoflurane-treated mice spent significantly less time exploring a novel object at 1 h but not at 24 h after the training phase. The deficit in short-term memory was reversed by the administration of ciproxifan 30 min before behavioral training.Conclusion
Isoflurane exposure induces reversible deficits in object recognition memory. Ciproxifan appears to be a potential therapeutic agent for improving post-anesthesia cognitive memory performance.64.
Antibody GD3G7 selected against embryonic glycosaminoglycans defines chondroitin sulfate-E domains highly up-regulated in ovarian cancer and involved in vascular endothelial growth factor binding 总被引:1,自引:0,他引:1 下载免费PDF全文
ten Dam GB van de Westerlo EM Purushothaman A Stan RV Bulten J Sweep FC Massuger LF Sugahara K van Kuppevelt TH 《The American journal of pathology》2007,171(4):1324-1333
Chondroitin sulfate (CS) is abundantly present in the tumor stroma, and tumor-specific CS modifications might be potential targets to influence tumor development. We applied the phage display technology to select antibodies that identify these tumor-specific CS modifications. Antibody GD3G7 was selected against embryonic glycosaminoglycans, and it reacted strongly with CS-E (rich in GlcA-GalNAc4S6S units). In ovarian adenocarcinomas, strong expression of this CS-E epitope was found in the extracellular matrix, and occasionally on tumor cells. No expression was found in normal ovary and cystadenomas. Differential expression was found in ovarian carcinoma cell lines, which correlated with the gene expression of the GalNAc4S-6st enzyme, involved in biosynthesis of CS-E. Vascular endothelial growth factor (VEGF)-sensitive fenestrated (in normal tissues) and tumor blood vessels were both identified by antibody GD3G7, which might implicate a role for CS-E in VEGF biology. VEGF bound to CS-E and antibody GD3G7 could compete for binding of VEGF to CS-E. In conclusion, antibody GD3G7 identified rare CS-E-like structures that were strongly expressed in ovarian adenocarcinomas. This antibody might therefore be instrumental for identifying tumor-related CS alterations. 相似文献
65.
66.
BACKGROUND: Dentists need to be aware of soft-tissue lesions resulting from cosmetic facial/lip procedures that involve the use of injectable materials. Common side effects detected on clinical examination may include edema, bruising and noninflammatory lip nodules. CASE DESCRIPTION: A 51-year-old woman visited a dental clinic with the chief complaint of a lump on the mucosal aspect of her lower lip. She reported having noted the lesion a few weeks before seeking care at the clinic. Several weeks later, the lesion persisted and new lesions were detected. The clinician excised the initial lesion only. CLINICAL IMPLICATIONS: The lip nodules were associated with a cosmetic procedure and were inflammatory in nature. This is the first granulomatous response reported as a result of injections with calcium hydroxylapatite (Radiesse, BioForm Medical, San Mateo, Calif.). Poor patient recollection of his or her medical history may result in confusion with pathological processes such as infection, neoplasia or malignancy. 相似文献
67.
Jozef Verbelen Henk Hoeksema Alexander Heyneman Ali Pirayesh Stan Monstrey 《Burns : journal of the International Society for Burn Injuries》2014
Introduction
Studies comparing contemporary silver dressings in burns are scarce.Methods
In a prospective, randomized, controlled study, counting 50 patients/research group, we compared two frequently used silver dressings, Acticoat™ and Aquacel® Ag, in the management of partial thickness burns with a predicted healing time between 7 and 21 days as assessed by laser Doppler imaging between 48 and 72 h after burn. Variables investigated were related to baseline research group characteristics, wound healing, bacteriology, economics, nurse, and patient experience.Results
Both research groups were comparably composed taking into account gender, age and burn characteristics. Similar results were obtained as to healing time and bacterial control with both silver dressings. A statistically significant difference in favor of the Aquacel® Ag dressing was found for average ease of use (p < 0.001), average ease of application (p = 0.001), patient pain (p < 0.001), patient comfort with the dressing (p = 0.017), silver staining (p < 0.001), and cost effectiveness (p < 0.001).Conclusion
Both silver dressings resulted in comparable healing times and bacterial control but the Aquacel® Ag dressing significantly increased comfort for patients as well as nurses and was significantly more cost-effective than the Acticoat™ dressing for the given indication. 相似文献68.
69.
70.
Lisa Adelfinger Rostislav Turecek Klara Ivankova Anders A. Jensen Stephen J. Moss Martin Gassmann Bernhard Bettler 《Biochemical pharmacology》2014
GABAB receptors assemble from GABAB1 and GABAB2 subunits. GABAB2 additionally associates with auxiliary KCTD subunits (named after their K+ channel tetramerization-domain). GABAB receptors couple to heterotrimeric G-proteins and activate inwardly-rectifying K+ channels through the βγ subunits released from the G-protein. Receptor-activated K+ currents desensitize in the sustained presence of agonist to avoid excessive effects on neuronal activity. Desensitization of K+ currents integrates distinct mechanistic underpinnings. GABAB receptor activity reduces protein kinase-A activity, which reduces phosphorylation of serine-892 in GABAB2 and promotes receptor degradation. This form of desensitization operates on the time scale of several minutes to hours. A faster form of desensitization is induced by the auxiliary subunit KCTD12, which interferes with channel activation by binding to the G-protein βγ subunits. Here we show that the two mechanisms of desensitization influence each other. Serine-892 phosphorylation in heterologous cells rearranges KCTD12 at the receptor and slows KCTD12-induced desensitization. Likewise, protein kinase-A activation in hippocampal neurons slows fast desensitization of GABAB receptor-activated K+ currents while protein kinase-A inhibition accelerates fast desensitization. Protein kinase-A fails to regulate fast desensitization in KCTD12 knock-out mice or knock-in mice with a serine-892 to alanine mutation, thus demonstrating that serine-892 phosphorylation regulates KCTD12-induced desensitization in vivo. Fast current desensitization is accelerated in hippocampal neurons carrying the serine-892 to alanine mutation, showing that tonic serine-892 phosphorylation normally limits KCTD12-induced desensitization. Tonic serine-892 phosphorylation is in turn promoted by assembly of receptors with KCTD12. This cross-regulation of serine-892 phosphorylation and KCTD12 activity sharpens the response during repeated receptor activation. 相似文献