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961.
Cynthia Chen Isaac Sia Hon-ming Ma Bee Choo Tai Angela Cheong Ngan Phoon Fong Shi Yu Julia Tan Kin Ming Chan Boon Yeow Tan Edward Menon Chye Hua Ee Kok Keng Lee Yee Sien Ng Yik Ying Teo Stefan Ma Derrick Heng Gerald Choon-Huat Koh 《PloS one》2014,9(8)
Objectives
The relationship between disability and comorbidity on mortality is widely perceived as additive in clinical models of frailty.Design
National data were retrospectively extracted from medical records of community hospital.Data Sources
There were of 12,804 acutely-disabled patients admitted for inpatient rehabilitation in Singapore rehabilitation community hospitals from 1996 through 2005 were followed up for death till 31 December 2011.Outcome Measure
Cox proportional-hazards regression to assess the interaction of comorbidity and disability at discharge on all-cause mortality.Results
During a median follow-up of 10.9 years, there were 8,565 deaths (66.9%). The mean age was 73.0 (standard deviation: 11.5) years. Independent risk factors of mortality were higher comorbidity (p<0.001), severity of disability at discharge (p<0.001), being widowed (adjusted hazard ratio [aHR]: 1.38, 95% confidence interval [CI]:1.25–1.53), low socioeconomic status (aHR:1.40, 95%CI:1.29–1.53), discharge to nursing home (aHR:1.14, 95%CI:1.05–1.22) and re-admission into acute care (aHR:1.54, 95%CI:1.45–1.65). In the main effects model, those with high comorbidity had an aHR = 2.41 (95%CI:2.13–2.72) whereas those with total disability had an aHR = 2.28 (95%CI:2.12–2.46). In the interaction model, synergistic interaction existed between comorbidity and disability (p<0.001) where those with high comorbidity and total disability had much higher aHR = 6.57 (95%CI:5.15–8.37).Conclusions
Patients with greater comorbidity and disability at discharge, discharge to nursing home or re-admission into acute care, lower socioeconomic status and being widowed had higher mortality risk. Our results identified predictive variables of mortality that map well onto the frailty cascade model. Increasing comorbidity and disability interacted synergistically to increase mortality risk. 相似文献962.
Body Mass Index and Mortality in Korean Intensive Care Units: A Prospective Multicenter Cohort Study
So Yeon Lim Won-Il Choi Kyeongman Jeon Eliseo Guallar Younsuck Koh Chae-Man Lim Shin Ok Koh Sungwon Na Young-Joo Lee Seok Chan Kim Ick Hee Kim Je Hyeong Kim Jae Yeol Kim Jaemin Lim Chin Kook Rhee Sunghoon Park Ho Cheol Kim Jin Hwa Lee Jisook Park Gee Young Suh Validation of Simplified acute physiology score in Korean Intensive care unit study group the Korean study group on respiratory failure 《PloS one》2014,9(4)
Background
The level of body mass index (BMI) that is associated with the lowest mortality in critically ill patients in Asian populations is uncertain. We aimed to examine the association of BMI with hospital mortality in critically ill patients in Korea.Methods
We conducted a prospective multicenter cohort study of 3,655 critically ill patients in 22 intensive care units (ICUs) in Korea. BMI was categorized into five groups: <18.5, 18.5 to 22.9, 23.0 to 24.9 (the reference category), 25.0 to 29.9, and ≥30.0 kg/m2.Results
The median BMI was 22.6 (IQR 20.3 to 25.1). The percentages of patients with BMI<18.5, 18.5 to 22.9, 23.0 to 24.9, 25.0 to 29.9, and ≥30.0 were 12, 42.3, 19.9, 22.4, and 3.3%, respectively. The Cox-proportional hazard ratios with exact partial likelihood to handle tied failures for hospital mortality comparing the BMI categories <18.5, 18.5 to 22.9, 25.0 to 29.9, and ≥30.0 with the reference category were 1.13 (0.88 to 1.44), 1.03 (0.84 to 1.26), 0.96 (0.76 to 1.22), and 0.68 (0.43 to 1.08), respectively, with a highly significant test for trend (p = 0.02).Conclusions
A graded inverse association between BMI and hospital mortality with a strong significant trend was found in critically ill patients in Korea. 相似文献963.
Juan-Hua Quan Byung-Hun Kang Guang-Ho Cha Wei Zhou Young-Bok Koh Jung-Bo Yang Heon-Jong Yoo Min-A Lee Jae-Sook Ryu Heung-Tae Noh Jaeyul Kwon Young-Ha Lee 《PloS one》2014,9(10)
To elucidate the roles of metalloproteinases and the Bcl-2 family of proteins in Trichovaginalis. vaginalis-induced apoptosis in human cervical cancer cells (SiHa cells) and vaginal epithelial cells (MS74 cells), SiHa cells and MS74 cells were incubated with live T. vaginalis, T. vaginalis excretory and secretory products (ESP), and T. vaginalis lysates, either with or without the specific metalloproteinase inhibitor 1,10-phenanthroline (1,10-PT), and examined apoptotic events and Bcl-2 signaling. The live T. vaginalis and the T. vaginalis ESP induced the release of cytochrome c into the cytosol, the activation of caspase-3 and caspase-9, and the cleavage of PARP. Additionally, the live T. vaginalis, but not the T. vaginalis lysate, induced the cleavage of the proapoptotic Bim protein. The live T. vaginalis and the T. vaginalis ESP, but not the T. vaginalis lysate, induced the dose-dependent cleavage of the antiapoptotic Bcl-xL and Mcl-1 proteins and decreased the association levels of Bcl-xL/Bim and Mcl-1/Bim complexes. We performed gelatin zymography and casein-hydrolysis assays on the live T. vaginalis and the T. vaginalis ESP to identify the apoptosis-inducing factor. Both the live T. vaginalis and the ESP contained high levels of metalloproteinases, of which activities were significantly inhibited by 1,10-PT treatment. Furthermore, the 1,10-PT blocked the cleavage of Bcl-xL, Mcl-1, PARP, caspase-3, and caspase-9, as well as the release of cytochrome c into the cytosol, and it significantly increased the association levels of the Bcl-xL/Bim and Mcl-1/Bim protein complexes, returning them to normal levels. Our results demonstrate that T. vaginalis induces mitochondria-dependent apoptosis in SiHa cells through the dissociation of Bcl-xL/Bim and Mcl-1/Bim complexes and that the apoptosis is blocked by the metalloproteinase inhibitor 1,10-PT. These results expand our understanding of the role of metalloproteinases in T. vaginalis-induced apoptosis and the signaling pathway in trichomoniasis of the cervicovaginal epithelial cells. 相似文献
964.
Shin Watanabe Takahiro Horie Kazuya Nagao Yasuhide Kuwabara Osamu Baba Hitoo Nishi Naoya Sowa Michiko Narazaki Tetsuya Matsuda Genzou Takemura Hiromichi Wada Koji Hasegawa Takeshi Kimura Koh Ono 《PloS one》2014,9(9)
Background
The mechanism of cardiac energy production against sustained pressure overload remains to be elucidated.Methods and Results
We generated cardiac-specific kinase-dead (kd) calcium/calmodulin-dependent protein kinase kinase-β (CaMKKβ) transgenic (α-MHC CaMKKβkd TG) mice using α-myosin heavy chain (α-MHC) promoter. Although CaMKKβ activity was significantly reduced, these mice had normal cardiac function and morphology at baseline. Here, we show that transverse aortic binding (TAC) in α-MHC CaMKKβkd TG mice led to accelerated death and left ventricular (LV) dilatation and dysfunction, which was accompanied by significant clinical signs of heart failure. CaMKKβ downstream signaling molecules, including adenosine monophosphate-activated protein kinase (AMPK), were also suppressed in α-MHC CaMKKβkd TG mice compared with wild-type (WT) mice. The expression levels of peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α, which is a downstream target of both of CaMKKβ and calcium/calmodulin kinases, were also significantly reduced in α-MHC CaMKKβkd TG mice compared with WT mice after TAC. In accordance with these findings, mitochondrial morphogenesis was damaged and creatine phosphate/β-ATP ratios assessed by magnetic resonance spectroscopy were suppressed in α-MHC CaMKKβkd TG mice compared with WT mice after TAC.Conclusions
These data indicate that CaMKKβ exerts protective effects on cardiac adaptive energy pooling against pressure-overload possibly through phosphorylation of AMPK and by upregulation of PGC-1α. Thus, CaMKKβ may be a therapeutic target for the treatment of heart failure. 相似文献965.
Dynamic optimization: inverse analysis for the Yurchenko layout vault in women's artistic gymnastics
The use of dynamic optimization to compute the trajectory of joint torques is not popular due to the large amount of computation required, the choice of initial "guesstimates" of torque values and the mathematical sophistication required to understand the technique. Modern optimal control algorithms circumvent most of these objections to the method. It is our aim to demonstrate that the dynamic optimization technique is feasible for complex movements, using the Yurchenko layout vault as an example. A dynamic optimization method to compute joint torques so that the histories of the angular orientations of the model segments closely approximate the corresponding observed angular coordinate histories is demonstrated with the Yurchenko layout vault using an optimal control package. The objective function used is a measure of distance of fitted segment angles to the data, plus the distance of the fitted whole body centre of mass (CM), from the whole body CM computed from the data. Including the CM into the objective function, facilitates the optimization process so as to obtain a set of torques which reproduced the data. The paper shows that the approach works well for the task examined, that is, where the dynamics of the system change during a movement (impact to postflight). 相似文献
966.
967.
Peptide transport in plants 总被引:10,自引:0,他引:10
Recent completion of the Arabidopsis genome revealed that this organism has ten times more peptide transporters than any other sequenced organism (prokaryote or eukaryote). These transporters are found in three protein families: the ABC-type transporters; the di- and tripeptide transporters; and the newly described tetra- and pentapeptide oligopetide transporters. The abundance of these transporters suggests that they play diverse and important roles in plant growth and development. Possible substrates for these transporters include glutathione, gamma-glutamyl peptides, hormone-amino acid conjugates, phytosulfokine, peptide-like compounds and peptide phytotoxins. However, the exact role of peptide transport in plants is still undefined. 相似文献
968.
Takeuchi K Yokogawa M Matsuda T Sugai M Kawano S Kohno T Nakamura H Takahashi H Shimada I 《Structure (London, England : 1993)》2003,11(11):1381-1392
We have determined the binding site on agitoxin2 (AgTx2) to the KcsA K(+) channel by a transferred cross-saturation (TCS) experiment. The residues significantly affected in the TCS experiments formed a contiguous surface on AgTx2, and substitutions of the surface residues decreased the binding affinity to the KcsA K(+) channel. Based on properties of the AgTx2 binding site with the KcsA K(+) channel, we present a surface motif that is observed in pore-blocking toxins affecting the K(+) channel. Furthermore, we also explain the structural basis of the specificity of the K(+) channel to the toxins. The TCS method utilized here is applicable not only for the channels, which are complexed with other inhibitors, but also with a variety of regulatory molecules, and provides important information about their interface in solution. 相似文献
969.
970.
Xu X Nagarajan H Lewis NE Pan S Cai Z Liu X Chen W Xie M Wang W Hammond S Andersen MR Neff N Passarelli B Koh W Fan HC Wang J Gui Y Lee KH Betenbaugh MJ Quake SR Famili I Palsson BO Wang J 《Nature biotechnology》2011,29(8):735-741
Chinese hamster ovary (CHO)-derived cell lines are the preferred host cells for the production of therapeutic proteins. Here we present a draft genomic sequence of the CHO-K1 ancestral cell line. The assembly comprises 2.45 Gb of genomic sequence, with 24,383 predicted genes. We associate most of the assembled scaffolds with 21 chromosomes isolated by microfluidics to identify chromosomal locations of genes. Furthermore, we investigate genes involved in glycosylation, which affect therapeutic protein quality, and viral susceptibility genes, which are relevant to cell engineering and regulatory concerns. Homologs of most human glycosylation-associated genes are present in the CHO-K1 genome, although 141 of these homologs are not expressed under exponential growth conditions. Many important viral entry genes are also present in the genome but not expressed, which may explain the unusual viral resistance property of CHO cell lines. We discuss how the availability of this genome sequence may facilitate genome-scale science for the optimization of biopharmaceutical protein production. 相似文献