全文获取类型
收费全文 | 114131篇 |
免费 | 11670篇 |
国内免费 | 6289篇 |
专业分类
耳鼻咽喉 | 977篇 |
儿科学 | 930篇 |
妇产科学 | 1376篇 |
基础医学 | 29943篇 |
口腔科学 | 3267篇 |
临床医学 | 7281篇 |
内科学 | 14313篇 |
皮肤病学 | 1985篇 |
神经病学 | 9805篇 |
特种医学 | 2092篇 |
外国民族医学 | 23篇 |
外科学 | 8723篇 |
综合类 | 16461篇 |
现状与发展 | 22篇 |
一般理论 | 2篇 |
预防医学 | 2881篇 |
眼科学 | 9274篇 |
药学 | 10718篇 |
17篇 | |
中国医学 | 3357篇 |
肿瘤学 | 8643篇 |
出版年
2024年 | 227篇 |
2023年 | 1366篇 |
2022年 | 2546篇 |
2021年 | 3617篇 |
2020年 | 3499篇 |
2019年 | 3044篇 |
2018年 | 3236篇 |
2017年 | 3674篇 |
2016年 | 4213篇 |
2015年 | 4645篇 |
2014年 | 7052篇 |
2013年 | 8782篇 |
2012年 | 6742篇 |
2011年 | 7815篇 |
2010年 | 6453篇 |
2009年 | 6170篇 |
2008年 | 6510篇 |
2007年 | 6399篇 |
2006年 | 6009篇 |
2005年 | 5109篇 |
2004年 | 4300篇 |
2003年 | 3559篇 |
2002年 | 2708篇 |
2001年 | 2310篇 |
2000年 | 1970篇 |
1999年 | 1731篇 |
1998年 | 1657篇 |
1997年 | 1525篇 |
1996年 | 1358篇 |
1995年 | 1433篇 |
1994年 | 1288篇 |
1993年 | 1115篇 |
1992年 | 942篇 |
1991年 | 879篇 |
1990年 | 757篇 |
1989年 | 763篇 |
1988年 | 656篇 |
1987年 | 592篇 |
1986年 | 553篇 |
1985年 | 871篇 |
1984年 | 730篇 |
1983年 | 544篇 |
1982年 | 656篇 |
1981年 | 524篇 |
1980年 | 425篇 |
1979年 | 327篇 |
1978年 | 236篇 |
1977年 | 169篇 |
1976年 | 162篇 |
1975年 | 57篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
2.
《Neuromodulation》2021,24(8):1422-1428
ObjectivesA recent approach to treatment of cluster headaches (CH) employs a microstimulator device for on-demand neuromodulation of the sphenopalatine ganglion (SPG) during an acute CH attack. A precise anatomical localization of the SPG within the pterygopalatine fossa (PPF) is optimal in order to position the SPG electrode array. This study aims to investigate a novel approach for SPG localization using computed tomography angiographic studies (CTA).Materials and MethodsTwo independent observers identified the location of the SPG on 54 computed tomography angiographic studies (CTA) and measured its position relative to the vidian canal (VC). The qualitative confidence of identification, morphology, position within the PPF and its relation to vascular structures were also recorded.ResultsThe SPG was detectable in 88% of cases with a variable position. The most frequent positions were superior (56%) and lateral (99%) relative to the VC with a mean (±SD) craniocaudal distance of 0.34 mm (±1.38) and a mean mediolateral distance of 3.04 mm (±1.2). However, in a considerable proportion of cases, the SPG was identified inferiorly to the VC (33%). Interobserver and intraobserver agreement for SPG location were moderate and strong respectively.ConclusionsSince localization of SPG on CTAs is feasible and reproducible, it has future clinical potential to aid placement, optimal positioning and individualized programming of the electrode array. 相似文献
3.
Patrick W. Keeley Mikayla C. Lebo Jordan D. Vieler Jason J. Kim Ace J. St. John Benjamin E. Reese 《The Journal of neuroscience》2021,41(1):103
Amacrine cells of the retina are conspicuously variable in their morphologies, their population demographics, and their ensuing functions. Vesicular glutamate transporter 3 (VGluT3) amacrine cells are a recently characterized type of amacrine cell exhibiting local dendritic autonomy. The present analysis has examined three features of this VGluT3 population, including their density, local distribution, and dendritic spread, to discern the extent to which these are interrelated, using male and female mice. We first demonstrate that Bax-mediated cell death transforms the mosaic of VGluT3 cells from a random distribution into a regular mosaic. We subsequently examine the relationship between cell density and mosaic regularity across recombinant inbred strains of mice, finding that, although both traits vary across the strains, they exhibit minimal covariation. Other genetic determinants must therefore contribute independently to final cell number and to mosaic order. Using a conditional KO approach, we further demonstrate that Bax acts via the bipolar cell population, rather than cell-intrinsically, to control VGluT3 cell number. Finally, we consider the relationship between the dendritic arbors of single VGluT3 cells and the distribution of their homotypic neighbors. Dendritic field area was found to be independent of Voronoi domain area, while dendritic coverage of single cells was not conserved, simply increasing with the size of the dendritic field. Bax-KO retinas exhibited a threefold increase in dendritic coverage. Each cell, however, contributed less dendrites at each depth within the plexus, intermingling their processes with those of neighboring cells to approximate a constant volumetric density, yielding a uniformity in process coverage across the population.SIGNIFICANCE STATEMENT Different types of retinal neuron spread their processes across the surface of the retina to achieve a degree of dendritic coverage that is characteristic of each type. Many of these types achieve a constant coverage by varying their dendritic field area inversely with the local density of like-type neighbors. Here we report a population of retinal amacrine cells that do not develop dendritic arbors in relation to the spatial positioning of such homotypic neighbors; rather, this cell type modulates the extent of its dendritic branching when faced with a variable number of overlapping dendritic fields to approximate a uniformity in dendritic density across the retina. 相似文献
4.
Bortezomib is a novel proteasome inhibitor, which has been successfully used to treat mantle cell lymphoma and multiple myeloma. However, the direct effects of bortezomib on acute promyelocytic leukaemia (APL) have not been fully investigated. In the present study, the WST-8 assay, western blotting, flow cytometry, monodansylcadaverine staining and transmission electron microscopy were performed. It was demonstrated that bortezomib treatment induced a time- and dose-dependent decrease in the viability of NB4 cells. Bortezomib treatment induced cell apoptosis in NB4 cells, as assessed by Annexin V/propidium iodide analysis, and the detection of cleaved caspase-3, cleaved poly(ADP-ribose) polymerase, Bax and Bcl-2 expression. Furthermore, bortezomib treatment induced autophagy in NB4 cells, as indicated by autophagosome formation, p62 degradation, LC3-I to LC3-II conversion and formation of acidic autophagic vacuoles. Notably, autophagy induced by bortezomib was initiated prior to apoptosis. Inhibition of autophagy by knocking down Beclin-1 expression increased bortezomib-induced apoptosis in NB4 cells. Therefore, the present study revealed that the combination of bortezomib and autophagy inhibition may be a potential treatment strategy for APL. 相似文献
5.
6.
Gut bacteria and gut barrier plays important roles in body homeostasis. Ciprofloxacin (CPFX) is widely used to treat bacterial infections. However, whether high dosage of CPFX has side effects on gut barrier integrity is still unclear. Our results indicated that the High CPFX treatment (1 mg/ml) caused weight loss, nervousness, anorexia, and increased apoptosis cells in gut, but less influence was observed in the Low CPFX group (0.2 mg/ml). Meanwhile, the High CPFX treatment impaired tight junction molecules Ocln/ZO-1 level and down-regulated antibacterial genes expression (reg3γ, pla2g2α and defb1). Further, the High CPFX treatment increased pro-inflammatory cytokine IL-1β in intestinal tract, decreased IL-17A of duodenum but increased IL-17A of colon at day 37. In addition, the gut bacterial diversity and richness behaved significantly loss regarding CPFX treatment, especially in the High CPFX group during the experiment. Indole exhibited sharply decline in both Low and High CPFX groups at day 7, and the High CPFX mice needed longer time on restoring indole level. Meanwhile, CPFX treatment strongly decreased the concentrations of butyric acid and valeric acid at day 1. Correlation analysis indicated that the linked patterns between the key bacteria (families Bacteroidales_S247, Ruminococcaceae and Desulfovibrionaceae) and metabolites (indole and butyric acid) were disturbed via the CPFX treatment. In conclusion, the High CPFX treatment impaired the gut barrier with the evidence of reduced expression of tight junction proteins, increased apoptosis cells and inflammatory cells, decreased the bacterial diversity and composition, which suggesting a proper antibiotic-dosage use should be carefully considered in disease treatment. 相似文献
7.
《Biomedical and environmental sciences : BES》2020,33(5):295-305
Objective Interferon-induced transmembrane protein 3(IFITM3) is an important member of the IFITM family. However, the molecular mechanisms underlying its antiviral action have not been completely elucidated. Recent studies on IFITM3, particularly those focused on innate antiviral defense mechanisms, have shown that IFITM3 affects the body's adaptive immune response. The aim of this study was to determine the contribution of IFITM3 proteins to immune control of influenza infection in vivo.Methods We performed proteomics, flow cytometry, and immunohistochemistry analysis and used bioinformatics tools to systematically compare and analyze the differences in natural killer(NK) cell numbers, their activation, and their immune function in the lungs of Ifitm3-/-and wild-type mice.Results Ifitm3-/-mice developed more severe inflammation and apoptotic responses compared to wild-type mice. Moreover, the NK cell activation was higher in the lungs of Ifitm3-/-mice during acute influenza infection.Conclusions Based on our results, we speculate that the NK cells are more readily activated in the absence of IFITM3, increasing mortality in Ifitm3-/-mice. 相似文献
8.
Many nanoparticles (NPs) have toxic effects on multiple cell lines. This toxicity is assumed to be related to their accumulation within cells. However, the process of internalization of NPs has not yet been fully characterized. In this study, the cellular uptake, accumulation, and localization of titanium dioxide nanoparticles (TiO2 NPs) in rat (C6) and human (U373) glial cells were analyzed using time-lapse microscopy (TLM) and transmission electron microscopy (TEM). Cytochalasin D (Cyt-D) was used to evaluate whether the internalization process depends of actin reorganization. To determine whether the NP uptake is mediated by phagocytosis or macropinocytosis, nitroblue tetrazolium (NBT) reduction was measured and the 5-(N-ethyl-N-isopropyl)-amiloride was used. Expression of proteins involved with endocytosis and exocytosis such as caveolin-1 (Cav-1) and cysteine string proteins (CSPs) was also determined using flow cytometry.TiO2 NPs were taken up by both cell types, were bound to cellular membranes and were internalized at very short times after exposure (C6, 30 min; U373, 2 h). During the uptake process, the formation of pseudopodia and intracellular vesicles was observed, indicating that this process was mediated by endocytosis. No specific localization of TiO2 NPs into particular organelles was found: in contrast, they were primarily localized into large vesicles in the cytoplasm. Internalization of TiO2 NPs was strongly inhibited by Cyt-D in both cells and by amiloride in U373 cells; besides, the observed endocytosis was not associated with NBT reduction in either cell type, indicating that macropinocytosis is the main process of internalization in U373 cells. In addition, increases in the expression of Cav-1 protein and CSPs were observed.In conclusion, glial cells are able to internalize TiO2 NPs by a constitutive endocytic mechanism which may be associated with their strong cytotoxic effect in these cells; therefore, TiO2 NPs internalization and their accumulation in brain cells could be dangerous to human health. 相似文献
9.
Jinju Wang Shuzhen Chen Wenfeng Zhang Yanfang Chen Ji C. Bihl 《CNS Neuroscience & Therapeutics》2020,26(12):1255
AimsWe previously showed that the protective effects of endothelial progenitor cells (EPCs)‐released exosomes (EPC‐EXs) on endothelium in diabetes. However, whether EPC‐EXs are protective in diabetic ischemic stroke is unknown. Here, we investigated the effects of EPC‐EXs on diabetic stroke mice and tested whether miR‐126 enriched EPC‐EXs (EPC‐EXsmiR126) have enhanced efficacy.MethodsThe db/db mice subjected to ischemic stroke were intravenously administrated with EPC‐EXs 2 hours after ischemic stroke. The infarct volume, cerebral microvascular density (MVD), cerebral blood flow (CBF), neurological function, angiogenesis and neurogenesis, and levels of cleaved caspase‐3, miR‐126, and VEGFR2 were measured on day 2 and 14.ResultsWe found that (a) injected EPC‐EXs merged with brain endothelial cells, neurons, astrocytes, and microglia in the peri‐infarct area; (b) EPC‐EXsmiR126 were more effective than EPC‐EXs in decreasing infarct size and increasing CBF and MVD, and in promoting angiogenesis and neurogenesis as well as neurological functional recovery; (c) These effects were accompanied with downregulated cleaved caspase‐3 on day 2 and vascular endothelial growth factor receptor 2 (VEGFR2) upregulation till day 14.ConclusionOur results indicate that enrichment of miR126 enhanced the therapeutic efficacy of EPC‐EXs on diabetic ischemic stroke by attenuating acute injury and promoting neurological function recovery. 相似文献
10.
Hsiao-Hsuan Kuo Ran Fan Nina Dvorina Andres Chiesa-Vottero William M. Baldwin III 《Journal of the American Society of Nephrology : JASN》2015,26(4):855-863
Antibody-mediated rejection is a major complication in renal transplantation. The pathologic manifestations of acute antibody-mediated rejection that has progressed to functional impairment of a renal transplant have been defined in clinical biopsy specimens. However, the initial stages of the process are difficult to resolve with the unavoidable variables of clinical studies. We devised a model of renal transplantation to elucidate the initial stages of humoral rejection. Kidneys were orthotopically allografted to immunodeficient mice. After perioperative inflammation subsided, donor-specific alloantibodies were passively transferred to the recipient. Within 1 hour after a single transfer of antibodies, C4d was deposited diffusely on capillaries, and von Willebrand factor released from endothelial cells coated intravascular platelet aggregates. Platelet-transported inflammatory mediators platelet factor 4 and serotonin accumulated in the graft at 100- to 1000-fold higher concentrations compared with other platelet-transported chemokines. Activated platelets that expressed P-selectin attached to vascular endothelium and macrophages. These intragraft inflammatory changes were accompanied by evidence of acute endothelial injury. Repeated transfers of alloantibodies over 1 week sustained high levels of platelet factor 4 and serotonin. Platelet depletion decreased platelet mediators and altered the accumulation of macrophages. These data indicate that platelets augment early inflammation in response to donor-specific antibodies and that platelet-derived mediators may be markers of evolving alloantibody responses. 相似文献