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61.
Duff RM Tay V Hackman P Ravenscroft G McLean C Kennedy P Steinbach A Schöffler W van der Ven PF Fürst DO Song J Djinović-Carugo K Penttilä S Raheem O Reardon K Malandrini A Gambelli S Villanova M Nowak KJ Williams DR Landers JE Brown RH Udd B Laing NG 《American journal of human genetics》2011,(6):79-740
Linkage analysis of the dominant distal myopathy we previously identified in a large Australian family demonstrated one significant linkage region located on chromosome 7 and encompassing 18.6 Mbp and 151 genes. The strongest candidate gene was FLNC because filamin C, the encoded protein, is muscle-specific and associated with myofibrillar myopathy. Sequencing of FLNC cDNA identified a c.752T>C (p.Met251Thr) mutation in the N-terminal actin-binding domain (ABD); this mutation segregated with the disease and was absent in 200 controls. We identified an Italian family with the same phenotype and found a c.577G>A (p.Ala193Thr) filamin C ABD mutation that segregated with the disease. Filamin C ABD mutations have not been described, although filamin A and filamin B ABD mutations cause multiple musculoskeletal disorders. The distal myopathy phenotype and muscle pathology in the two families differ from myofibrillar myopathies caused by filamin C rod and dimerization domain mutations because of the distinct involvement of hand muscles and lack of pathological protein aggregation. Thus, like the position of FLNA and B mutations, the position of the FLNC mutation determines disease phenotype. The two filamin C ABD mutations increase actin-binding affinity in a manner similar to filamin A and filamin B ABD mutations. Cell-culture expression of the c.752T>C (p.Met251)Thr mutant filamin C ABD demonstrated reduced nuclear localization as did mutant filamin A and filamin B ABDs. Expression of both filamin C ABD mutants as full-length proteins induced increased aggregation of filamin. We conclude filamin C ABD mutations cause a recognizable distal myopathy, most likely through increased actin affinity, similar to the pathological mechanism of filamin A and filamin B ABD mutations. 相似文献
62.
The purpose of this study is to investigate unique features of body segments in fall and activities of daily living (ADL) to make automatic detection of fall in its descending phase before the impact. Thus, fall-related injuries can be prevented or reduced by deploying feedback systems before the impact. In this study, the authors propose the following hypothesis: (1) thigh segment normally does not go beyond certain threshold angle to forward and sideways directions in ADL and (2) even if it does, the angular characteristics measured at torso and thigh differ from one another in ADL whereas in the case of fall, they become congruent. These two factors can be used to distinguish fall from ADL in its inception. Vicon 3-D motion analysis system was used in this study. High level of correlation between thigh and torso segments (corr > 0.99) was found for fall activities and low correlation coefficients (mean corr for lateral movements is 0.2338 and for sagittal movements is -0.665) were observed in ADL. By applying the hypothesis, all simulated falls could be detected with no false alarms and around 700ms lead-time before the impact was achieved in pre-impact fall detection. It is the longest lead-time obtained so far in pre-impact fall detection. 相似文献
63.
This study isolated nine strains of aerobic phenol-degrading granules. These isolates (I1–I9) were characterized using 16S
rRNA gene sequencing, with γ-Proteobacteria as the dominant strains in the aerobic granules. While most strains demonstrated either high phenol-degrading capabilities
or auto-aggregation capabilities, three isolates, I2, I6, and I8 showed both features. These findings contradict the previous
view that auto-aggregation and phenol degradation are mutually exclusive in aerobic granules. Strains I2 and I8 independently
formed single-culture aerobic granules except for I3. Anti-microbial activity test results indicated that strains I2 and I8
inhibited growth of strain I3. However, co-culturing I3 with I2 or I8 helped to form granules. 相似文献
64.
65.
66.
Influence of starvation time on formation and stability of aerobic granules in sequencing batch reactors 总被引:3,自引:0,他引:3
Three sequencing batch reactors, R1, R2 and R3, with a 1.5-h, 4-h and 8-h cycle time, respectively, were used to cultivate aerobic granules with the same synthetic wastewater containing 1000 mg l(-1) COD. As the initial COD concentrations in the cycles were the same, three different cycle times led to three different starvation times in repeated cycles of the three reactors. It was found that 63 cycles were needed to form granules with the longest starvation time in R3 while it took 256 cycles in R1 with the shortest starvation time. However, as far as the formation time was concerned, granules were formed on day 16 with 1.5-h cycle time while on day 21 with 8-h cycle time, which indicated that a shorter cycle time with a shorter starvation time speeded up the granulation. This was mainly due to the stronger hydraulic selection pressure at shorter cycle time. However, it was found that granules formed with cycle time of 1.5h were unstable. Fluffy granules with poor settling ability were observed in R1 in the 4th month, which led to the collapse of R1 after 160-day of operation. Granules in R2 and R3 showed good stability during the long-term operation. Therefore, a reasonable starvation time was necessary to maintain the long-term stability of aerobic granules. 相似文献
67.
68.
Background
Although there is a growing body of evidence showing that patients with type 2 diabetes mellitus (T2DM) have poor glycemic control in general, it is not clear whether T2DM patients with pre-existing cardiovascular diseases (CVD) are more or less likely to have good glycemic control than patients without pre-existing CVD. Our aim was to examine the degree of glycemic control among T2DM patients in Europe with and without pre-existing CVD.Methods
This is a matched cohort study based on a multi-center, observational study with retrospective medical chart reviews of T2DM patients in Spain, France, United Kingdom, Norway, Finland, Germany, and Poland. Included patients were aged >= 30 years at time of diagnosis of T2DM, had added a SU or a PPARγ agonist to failing metformin monotherapy (index date) and had pre-existing CVD (cases). A control cohort with T2DM without pre-existing CVD was identified using 1:1 propensity score matching. With difference-in-difference approach, logistic and linear regression analyses were applied to identify differences in glycemic control by CVD during the follow up period, after controlling for baseline demographics, clinical information, and concurrent anti-hyperglycemic medication use.Results
The percentage of case patients with adequate glycemic control relative to control patients during the 1st, 2nd, 3rd, and 4th years after the index date was 19.9 vs. 26.5, 16.8 vs. 26.5, 18.8 vs. 28.3, and 16.8 vs. 23.5 respectively. Cases were significantly less likely to have adequate glycemic control (odds ratio: 0.62; 95% confidence interval: 0.46-0.82) than controls after adjusting for baseline differences, secular trend, and other potential confounding covariates.Conclusions
T2DM patients with pre-existing CVD tended to have poorer glycemic control than those without pre-existing CVD, all other factors being equal. It suggests that clinicians may need to pay more attention to glycemic control among T2DM patients with CVD. 相似文献69.
Mutant template human telomerase RNAs (MT-hTers) have been shown to induce apoptosis in various cancer cells with high telomerase activity. However, the mechanism by which MT-hTers inhibit the growth of cancer cells and their effects on normal cells remain unknown. To determine the effects of MT-hTers on normal cells, MT-hTer-47A and -AU5 were introduced into IMR90 lung fibroblasts, which have low telomerase levels. Growth of IMR90 cells after MT-hTers infection was not significantly impaired; however, similar treatments in telomerase-overexpressing IMR90 [IMR90 wild-type (WT)hTERT] cells inhibited cell proliferation and induced apoptosis. Confocal microscopy showed that MT-hTers induced DNA damage foci (i.e. 53BP1 and γ-H2AX) in IMR90 WThTERT cells. Microarray analysis revealed that GADD45γ was significantly elevated in MT-hTer-treated IMR90 WThTERT cells. MT-hTers also induced ATM phosphorylation at Ser1981 in IMR90 WThTERT cells, and western blot analysis revealed high levels of phosphorylated p53 after the down-regulation of cellular TRF2 expression in MT-hTer-treated IMR90 WThTERT cells. Taken together, we have shown that MT-hTers induce double-stranded DNA break-like damages in telomerase positive IMR90 WThTERT cells after phosphorylation of ATM and p53 via suppression of TRF2, which may eventually lead to apoptosis via elevation of GADD45γ. 相似文献
70.
An electron microscopic study of neuronal degeneration and glial cell reaction in the retina of glaucomatous rats 总被引:2,自引:0,他引:2
The present investigation was focused on the ultrastructural changes in the neurons and glial cells in the retina of rats with experimentally-induced glaucoma. An experimental glaucoma model was created by limbal-derived vein cauterization. Animals were sacrificed at 1, 3 weeks and 3 months post-operation. Retinae were dissected and processed for electron microscopy. Neuronal degeneration was observed in all the different layers of the retina at both 1 and 3 weeks post-operation. Some degenerating neurons were found in the ganglion cell layer (GCL), inner nuclear layer (INL) and outer nuclear layer (ONL). And the dying neurons presented apoptotic-like more than necrotic neurons. Many degenerating axons and axon terminals were observed between neurons in the GCL, inner plexiform layer (IPL), INL, and outer plexiform layer (OPL). Activated astrocytes and microglial cells were present in close association with degenerating neurons and axons. The Müller cells in the INL also presented longer and darker processes with more microfilaments than in normal cells. Degenerating neuronal debris, degenerating axonal profiles and electron-dense bodies were often found in the cytoplasm of macrophages. The results suggest that both microglial cells and astrocytes are activated in the process of neuronal degeneration in the retina of experimentally-induced glaucomatous rats. It is hypothesized that they may play a protective role in removing degenerating neuronal elements in the retina after the onset of glaucoma. 相似文献