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排序方式: 共有565条查询结果,搜索用时 15 毫秒
61.
AL Burgueño TF Gianotti NG Mansilla CJ Pirola S Sookoian 《Clinical science (London, England : 1979)》2013,124(1):53-63
CVD (cardiovascular disease) is associated with abnormal liver enzymes, and NAFLD (non-alcoholic fatty liver disease) is independently associated with cardiovascular risk. To gain insights into the molecular events underlying the association between liver enzymes and CVD, we developed an HFD (high-fat diet)-induced NAFLD in the SHR (spontaneously hypertensive rat) and its control WKY (Wistar-Kyoto) rat strain. We hypothesized that hepatic induction of Hif1a (hypoxia-inducible factor 1α) might be the link between CVD and liver injury. Male SHRs (n=13) and WKY rats (n=14) at 16?weeks of age were divided into two experimental groups: standard chow diet and HFD (10?weeks). HFD-fed rats, irrespective of the strain, developed NAFLD; however, only HFD-SHRs had focus of lobular inflammation and high levels of hepatic TNFα (tumour necrosis factor α). SHRs had significantly higher liver weight and ALT (alanine aminotransferase) levels, irrespective of NAFLD. Liver abundance of Hif1a mRNA and Hif1α protein were overexpressed in SHRs (P<0.04) and were significantly correlated with ALT levels (R=0.50, P<0.006). This effect was not reverted by a direct acting splanchnic vasodilator (hydralazine). Angiogenesis may be induced by the HFD, but the disease model showed significantly higher hepatic Vegf (vascular endothelial growth factor) levels (P<0.025) even in absence of dietary insult. Hif1a mRNA overexpression was not observed in other tissues. Liver mRNA of Nr1d1 (nuclear receptor subfamily 1, group D, member 1; P<0.04), Ppara [Ppar (peroxisome-proliferatoractivated receptor) α; P<0.05], Pparg (Pparγ; P<0.001) and Sirt1 (Sirtuin 1; P<0.001) were significantly upregulated in SHRs, irrespective of NAFLD. Sirt1 and Hif1a mRNAs were significantly correlated (R=0.71, P<0.00002). In conclusion, CVD is associated with Hif1a-related liver damage, hepatomegaly and reprogramming of liver metabolism, probably to compensate metabolic demands. 相似文献
62.
Julio González Martín-Moro Marco Sales-Sanz Noelia Oblanca-Llamazares Angel Bustos-García Jose Carlos Méndez-Cendón Eduardo Fandiño 《Orbit (Amsterdam, Netherlands)》2018,37(4):306-308
A 47-year-old woman was diagnosed with dural carotid cavernous fistula (CCF) in her right eye (RE). Scans of the choroid using Spectralis optic coherence tomography (OCT) demonstrated significant asymmetry in subfoveal choroidal thickness (RE 451 μm, left eye (LE) 367 μm). This asymmetry disappeared after the fistula was embolizated through the ophthalmic artery (RE 341 μm; LE 340 μm). This case suggests that OCT should be considered as an ancillary test in the diagnosis of CCF. 相似文献
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64.
Kunzevitzky NJ Almeida MV Duan Y Li S Xiang M Goldberg JL 《Molecular and cellular neurosciences》2011,46(4):731-741
The regulation of retinal ganglion cell (RGC) axon growth and patterning in vivo is thought to be largely dependent on interactions with visual pathway and target cells. Here we address the hypothesis that amacrine cells, RGCs' presynaptic partners, regulate RGC axon growth or targeting. We asked whether amacrine cells play a role in RGC axon growth in vivo using Foxn4(-/-) mice, which have fewer amacrine cells, but a normal complement of RGCs. We found that Foxn4(-/-) mice have a similar reduction in most subtypes of amacrine cells examined. Remarkably, spontaneous retinal waves were not affected by the reduction of amacrine cells in the Foxn4(-/-) mice. There was, however, a developmental delay in the distribution of RGC projections to the superior colliculus. Furthermore, RGC axons failed to penetrate into the retinorecipient layers in the Foxn4(-/-) mice. Foxn4 is not expressed by RGCs and was not detectable in the superior colliculus itself. These findings suggest that amacrine cells are critical for proper RGC axon growth in vivo, and support the hypothesis that the amacrine cell-RGC interaction may contribute to the regulation of distal projections and axon patterning. 相似文献
65.
Amal Yousfan Noelia Rubio Abdul Hakim Natouf Aamal Daher Nedal Al-Kafry Kerrie Venner Houmam Kafa 《RSC advances》2020,10(48):28992
The use of nanoparticles (NPs) for intranasal (IN) drug delivery to the brain represents a hopeful strategy to enhance brain targeting of anti-epileptic drugs. In the present work, chitosan–lecithin NPs loaded with phenytoin (PHT), were prepared using the nano-precipitation method. The spherical nature of the NPs and their stability were confirmed using scanning and transmission electron microscopy, while the average dynamic size and zeta potential were measured using dynamic light scattering. The encapsulation efficiency of PHT was higher than 60% for all prepared NPs. Release studies showed that the amount of released PHT was directly related to the amount of chitosan used. The optimum preparation, L10Ci+ was administered via the IN route, and the levels of PHT in the brain were measured in three-time points. Two experimental controls were given via the intraperitoneal (IP) and IN routes. The highest PHT amount reaching 1.01 ± 0.55% for L10Ci+, which was associated with a sustained release of PHT. These preliminary findings show that the IN delivery of PHT-loaded NPs is very promising for managing epilepsy. The direct nose-to-brain approach increases the safety margins of PHT, while the sustained release could improve patient compliance in a clinical setting.The use of nanoparticles (NPs) for intranasal (IN) drug delivery to the brain represents a hopeful strategy to enhance brain targeting of anti-epileptic drugs. 相似文献
66.
Enhancement of intranasal vaccination in mice with deglycosylated chain A ricin by LTR72, a novel mucosal adjuvant 总被引:2,自引:0,他引:2
Intranasal (i.n.) vaccination with two suboptimal doses of 8 microg of deglycosylated chain A ricin (DGCA) stimulated low anti-ricin ELISA IgG and neutralizing antibody responses and the vaccine was only marginally protective against a lethal ricin toxin aerosol challenge. However, in the presence of 4, 2, or 1 microg of the mucosal adjuvant LTR72, a mutant of the heat-labile enterotoxin of Escherichia coli, the low antibody response and protection were substantially enhanced. In comparison to the vaccination with DGCA alone, vaccination with DGCA in the presence of three dose levels of LTR72, the anti-ricin ELISA serum IgG geometric mean titer (GMT) was increased, respectively, 191-, 572-, and 51-fold for IgG; 91-, 93-, and 60-fold for IgG1; nine-, six-, and two-fold for IgG2a; zero-, two-, and zero-fold for IgA. The three dose levels of the adjuvant enhanced the anti-ricin ELISA immunoglobulin GMTs in the lung lavage 4-, 14-, and 7-fold for IgG; two-, five-, and six-fold for IgG1; two-, six-, and two-fold IgG2a; and zero-, three-, and zero-fold for IgA, respectively. Compared to GMT obtained with the aqueous vaccine (1:2), the 10% serum neutralizing antibody GMT for the three dose levels was enhanced 25-, 60-, and 62-fold, respectively while the 50% neutralizing antibody GMT was enhanced more than 3-, 19- and 10-fold. Only 20% of the mice immunized with DGCA survived the lethal whole body aerosol challenge with 5-10 LD50 ricin toxin, while in the presence of 4, 2, and 1 microg LTR72, 100, 100 and 90% of the vaccinated mice survived, respectively. Safety of administration of two doses of LTR72 is indicated by the absence of histopathological changes in every organ including the lung and the CNS of the mice during the vaccination and during 57 days of the study. In the nasal passages of the mice in the absence of DGCA, LTR72 caused a transient inflammation for less than 7 weeks without permanent epithelial changes. Administration of the adjuvant in the presence of DGCA did not cause additional changes. Compared to the surviving mice vaccinated with DGCA alone, administration of the mucosal adjuvant with DGCA in spite of the better efficacy did not attenuate the lung injury at a single time point (16 days post-challenge). In mice treated with high(er) dose of vaccine, histological examinations during longer observation period rather than at one time point could reveal a different pattern. 相似文献
67.
Plazas PV De Rosa MJ Gomez-Casati ME Verbitsky M Weisstaub N Katz E Bouzat C Elgoyhen AB 《British journal of pharmacology》2005,145(7):963-974
We have performed a systematic mutagenesis of three hydrophobic rings (17', 13' and 9') within transmembrane region (TM) 2 of the alpha9alpha10 nicotinic cholinergic receptor (nAChR) to a hydrophilic (threonine) residue and compared the properties of mutant receptors reconstituted in Xenopus laevis oocytes. Phenotypic changes in alpha9alpha10 mutant receptors were evidenced by a decrease in the desensitization rate, an increase in both the EC(50) for ACh as well as the efficacy of partial agonists and the reduction of the allosteric modulation by extracellular Ca(2+). Mutated receptors exhibited spontaneous openings and, at the single-channel level, an increased apparent mean open time with no major changes in channel conductance, thus suggesting an increase in gating of the channel as the underlying mechanism. Overall, the degrees of the phenotypes of mutant receptors were more overt in the case of the centrally located V13'T mutant. Based on the atomic model of the pore of the electric organ of the Torpedo ray, we can propose that the interactions of side chains at positions 13' and 9' are key ones in creating an energetic barrier to ion permeation. In spite of the fact that the roles of the TM2 residues are mostly conserved in the distant alpha9alpha10 member of the nAChR family, their mechanistic contributions to channel gating show significant differences when compared to other nAChRs. These differences might be originated from slight differential intramolecular rearrangements during gating for the different receptors and might lead each nAChR to be in tune with their physiological roles. 相似文献
68.
69.
Ibáñez MA Cenizo N Río L Sánchez A San Norberto E Brizuela JA Gutiérrez V Vaquero C 《European journal of radiology》2011,80(2):543-547
The objective of the work is to study the clinical and haemodynamic evolution, over 1 year, in patients with femoropopliteal arterial pathology treated by means of atherectomy with the SilverHawk device.