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481.
El Beheiry MH Heximer SP Voigtlaender-Bolz J Mazer CD Connelly KA Wilson DF Beattie WS Tsui AK Zhang H Golam K Hu T Liu E Lidington D Bolz SS Hare GM 《Journal of applied physiology (Bethesda, Md. : 1985)》2011,111(4):1125-1133
Acute β-blockade with metoprolol has been associated with increased mortality by undefined mechanisms. Since metoprolol is a relatively high affinity blocker of β(2)-adrenoreceptors, we hypothesized that some of the increased mortality associated with its use may be due to its abrogation of β(2)-adrenoreceptor-mediated vasodilation of microvessels in different vascular beds. Cardiac output (CO; pressure volume loops), mean arterial pressure (MAP), relative cerebral blood flow (rCBF; laser Doppler), and microvascular brain tissue Po(2) (G2 oxyphor) were measured in anesthetized mice before and after acute treatment with metoprolol (3 mg/kg iv). The vasodilatory dose responses to β-adrenergic agonists (isoproterenol and clenbuterol), and the myogenic response, were assessed in isolated mesenteric resistance arteries (MRAs; ~200-μm diameter) and posterior cerebral arteries (PCAs ~150-μm diameter). Data are presented as means ± SE with statistical significance applied at P < 0.05. Metoprolol treatment did not effect MAP but reduced heart rate and stroke volume, CO, rCBF, and brain microvascular Po(2), while concurrently increasing systemic vascular resistance (P < 0.05 for all). In isolated MRAs, metoprolol did not affect basal artery tone or the myogenic response, but it did cause a dose-dependent impairment of isoproterenol- and clenbuterol-induced vasodilation. In isolated PCAs, metoprolol (50 μM) impaired maximal vasodilation in response to isoproterenol. These data support the hypothesis that acute administration of metoprolol can reduce tissue oxygen delivery by impairing the vasodilatory response to β(2)-adrenergic agonists. This mechanism may contribute to the observed increase in mortality associated with acute administration of metoprolol in perioperative patients. 相似文献
482.
Critical limb ischaemia (CLI), due to atherosclerotic arterial occlusion, affects over 20,000 people per year in the United
Kingdom with many facing lower limb amputation and early death. A role for endothelin-1 (ET-1) in atherosclerosis is well-established
and increased circulating and tissue levels of this peptide have been detected in patients with CLI. ET-1 and its receptors
were identified in atherosclerotic popliteal arteries obtained from CLI patients undergoing lower limb amputation. In addition,
plasma ET-1 levels were compared with those of non-ischaemic controls. ET-1 was associated with regions of atherosclerotic
plaque, particularly in regions with high macrophage content. This peptide was also associated with endothelial cells lining
the main vessel lumen as well as adventitial microvessels. ETA and ETB receptors were located within regions of plaque, adventitial microvessels and perivascular nerves. There was a statistically
significant increase (P < 0.001) in plasma ET-1 in CLI patients when compared with controls. These results reveal sources of ET-1 in atherosclerotic
popliteal arteries that potentially contribute to increased circulating levels of this peptide. Identification of variable
receptor distributions in ischaemic tissue suggests a therapeutic potential of selective receptor targeting in patients with
CLI. 相似文献
483.
484.
Pan Junling Tsui Clement Li Mengxing Xiao Kun de Hoog G. Sybren Verweij Paul E. Cao Yu Lu Hongguang Jiang Yanping 《Mycopathologia》2020,185(3):555-567
Mycopathologia - Lichtheimia species are emerging opportunistic fungal pathogens in the Mucorales, causing serious skin and respiratory infections in immunocompromised patients. Established agents... 相似文献
485.
Chen‐Ting Kuo Guan‐Ting You Ying‐Jie Jian Ting‐Shin Chen Yu‐Chen Siao Ao‐Lin Hsu Tsui‐Ting Ching 《Aging cell》2020,19(6)
Stress granules (SGs) are nonmembranous organelles that are dynamically assembled and disassembled in response to various stressors. Under stressed conditions, polyadenylated mRNAs and translation factors are sequestrated in SGs to promote global repression of protein synthesis. It has been previously demonstrated that SG formation enhances cell survival and stress resistance. However, the physiological role of SGs in organismal aging and longevity regulation remains unclear. In this study, we used TIAR‐1::GFP and GTBP‐1::GFP as markers to monitor the formation of SGs in Caenorhabditis elegans. We found that, in addition to acute heat stress, SG formation could also be triggered by dietary changes, such as starvation and dietary restriction (DR). We found that HSF‐1 is required for the SG formation in response to acute heat shock and starvation but not DR, whereas the AMPK‐eEF2K signaling is required for starvation and DR‐induced SG formation but not heat shock. Moreover, our data suggest that this AMPK‐eEF2K pathway‐mediated SG formation is required for lifespan extension by DR, but dispensable for the longevity by reduced insulin/IGF‐1 signaling. Collectively, our findings unveil a novel role of SG formation in DR‐induced longevity. 相似文献
486.
The influence of sex of broilers and dietary phosphorus (P) level on energy utilization and apparent ileal digestibility of N, P and phytate-P were investigated. The AMEN was determined using 3- and 6-week old broilers, while the apparent ileal digestibility were determined only with 6-week old birds. Sex of broilers had no effect on the AMEN values determined during week 3. During week 6, the AMEN values for male broilers were higher (P?0.01) than those for the females. An interaction (P?0.05) between sex and dietary P level was also observed. AMEN values determined with male broilers were lower in the adequate-P diet compared to those in the low-P diet, whereas no effect of P level was observed in females. Female broilers tended (P?0.10) to have a higher ileal N digestibility than the males, but a significant (P?0.01) sex ×?P level interaction was observed. Males receiving the adequate-P diet had a lower N digestibility than those receiving the low-P diet, whereas the opposite was true in the females. Ileal phytate P degradation in males was higher than in females (0.282 vs. 0.234), but the differences were not significant. Increasing dietary P level increased ileal P digestibility in both the males and females, but the improvements were greater in the females, as indicated by a significant sex × P level interaction. 相似文献
487.
Bjorn?WH?van Heumen Hennie?MJ?Roelofs René?HM?te Morsche Fokko?M?Nagengast Wilbert?HM?PetersEmail author 《Orphanet journal of rare diseases》2013,8(1):181
Background
Familial adenomatous polyposis (FAP) is a disease characterized by the development of hundreds to thousands of adenomatous polyps in the colorectum early in life. Virtually all patients with FAP will develop colorectal cancer before the age of 40 to 50 years, unless prophylactic colectomy is performed, which significantly improves their prognosis. The mortality pattern has changed and duodenal cancer now is one of the main cancer-related causes of death in these patients. Practically all patients with FAP develop premalignant duodenal adenomas, which may develop to duodenal cancer in approximately 3-7% of patients. Duodenal cancer in patients with FAP has a poor prognosis. The clinical challenge is to identify patients at high-risk for duodenal carcinoma. Chemoprevention would be desirable to avoid duodenectomy. The main goal of this study is to identify risk markers in normal duodenal mucosa of patients with FAP, that could help identify patients at increased risk for malignant transformation.Methods
Messenger RNA (mRNA) levels of glutathione S-transferase A1 (GSTA1), glutathione S-transferase P1 (GSTP1), KIAA1199, E-cadherin, peroxisome proliferative activated receptor δ (PPARδ), caspase-3, cyclin D1, β-catenin, and cyclooxygenase-2 (COX-2) were measured in duodenal mucosa, using the QuantiGene 2.0 Plex assay. Levels in normal appearing mucosa of patients with FAP (n?=?37) were compared with levels in non-FAP patient controls (n?=?16). In addition, levels before and after treatment with either celecoxib & ursodeoxycholic acid (UDCA, n?=?14) or celecoxib & placebo (n?=?13) were evaluated in patients with FAP.Results
mRNA levels of glutathione S-transferase A1 (28.16% vs. 38.24%, p?=?0.008) and caspase-3 (3.30% vs. 5.31%, p?=?0.001) were significantly lower in patients with FAP vs. non-FAP patient controls, respectively. COX-2 mRNA levels in normal duodenal mucosa of patients with FAP were found to be unexpectedly low. None of the potential risk markers was influenced by celecoxib or celecoxib & UDCA.Conclusions
Protection against toxins and carcinogens (GSTA1) and apoptosis (caspase-3) is low in patients with FAP, which could contribute to increased susceptibility for malignant transformation of duodenal mucosa.Trial registration
http://ClinicalTrials.gov number NCT00808743488.
489.
Youssef Zaim Wadghiri Jialin Li Jinhuan Wang Dung Minh Hoang Yanjie Sun Hong Xu Wai Tsui Yongsheng Li Allal Boutajangout Andrew Wang Mony de Leon Thomas Wisniewski 《PloS one》2013,8(2)
Amyloid plaques are a key pathological hallmark of Alzheimer’s disease (AD). The detection of amyloid plaques in the brain is important for the diagnosis of AD, as well as for following potential amyloid targeting therapeutic interventions. Our group has developed several contrast agents to detect amyloid plaques in vivo using magnetic resonance microimaging (µMRI) in AD transgenic mice, where we used mannitol to enhance blood brain barrier (BBB) permeability. In the present study, we used bifunctional ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, chemically coupled with Aβ1-42 peptide to image amyloid plaque deposition in the mouse brain. We coupled the nanoparticles to polyethylene glycol (PEG) in order to improve BBB permeability. These USPIO-PEG-Aβ1-42 nanoparticles were injected intravenously in AD model transgenic mice followed by initial in vivo and subsequent ex vivo μMRI. A 3D gradient multi-echo sequence was used for imaging with a 100 µm isotropic resolution. The amyloid plaques detected by T2*-weighted μMRI were confirmed with matched histological sections. The region of interest-based quantitative measurement of T2* values obtained from the in vivo μMRI showed contrast injected AD Tg mice had significantly reduced T2* values compared to wild-type mice. In addition, the ex vivo scans were examined with voxel-based analysis (VBA) using statistical parametric mapping (SPM) for comparison of USPIO-PEG-Aβ1-42 injected AD transgenic and USPIO alone injected AD transgenic mice. The regional differences seen by VBA in the USPIO-PEG-Aβ1-42 injected AD transgenic correlated with the amyloid plaque distribution histologically. Our results indicate that USPIO-PEG-Aβ1-42 can be used for amyloid plaque detection in vivo by intravenous injection without the need to co-inject an agent which increases permeability of the BBB. This technique could aid the development of novel amyloid targeting drugs by allowing therapeutic effects to be followed longitudinally in model AD mice. 相似文献
490.