全文获取类型
收费全文 | 3810篇 |
免费 | 380篇 |
国内免费 | 275篇 |
专业分类
4465篇 |
出版年
2024年 | 8篇 |
2023年 | 33篇 |
2022年 | 69篇 |
2021年 | 151篇 |
2020年 | 100篇 |
2019年 | 148篇 |
2018年 | 146篇 |
2017年 | 121篇 |
2016年 | 165篇 |
2015年 | 264篇 |
2014年 | 275篇 |
2013年 | 292篇 |
2012年 | 364篇 |
2011年 | 320篇 |
2010年 | 209篇 |
2009年 | 187篇 |
2008年 | 230篇 |
2007年 | 199篇 |
2006年 | 162篇 |
2005年 | 137篇 |
2004年 | 138篇 |
2003年 | 125篇 |
2002年 | 117篇 |
2001年 | 66篇 |
2000年 | 52篇 |
1999年 | 53篇 |
1998年 | 26篇 |
1997年 | 20篇 |
1996年 | 24篇 |
1995年 | 16篇 |
1994年 | 20篇 |
1993年 | 20篇 |
1992年 | 22篇 |
1991年 | 14篇 |
1990年 | 17篇 |
1989年 | 9篇 |
1988年 | 13篇 |
1987年 | 10篇 |
1986年 | 16篇 |
1985年 | 6篇 |
1984年 | 12篇 |
1983年 | 11篇 |
1982年 | 5篇 |
1981年 | 5篇 |
1980年 | 7篇 |
1979年 | 4篇 |
1978年 | 6篇 |
1976年 | 8篇 |
1975年 | 10篇 |
1974年 | 9篇 |
排序方式: 共有4465条查询结果,搜索用时 15 毫秒
81.
Abstract Adenosine and guanosine analogs with 8-position vinyl and aryl groups were prepared by palladium catalyzed cross-coupling of organostannanes with 8-bromopurine nucleosides. The reaction conditions and catalyst composition were improved so that both vinyl and aryl modifications could be made by a general procedure. 相似文献
82.
Dandan Chen Fengxia Ma Shuxia Xu Shaoguang Yang Fang Chen Lijuan Rong Ying Chi Qinjun Zhao Shihong Lu Zhibo Han Aiming Pang Zhongchao Han 《Cytotherapy》2013,15(4):423-433
Background aimsToll-like receptors (TLRs) play an important role in innate and adaptive immunity by recognizing pathogen-associated molecular patterns (PAMPs).MethodsIn the present study, we investigated the expression and role of TLRs on human umbilical cord mesenchymal stromal cells (UC-MSCs). The proliferation, differentiation and immunoregulatory activity of UC-MSCs primed with or without TLR ligands were determined.ResultsAt the RNA level, the expression of TLR2, 4, 6 and 9 was relatively higher than that of other TLRs. However, TLR3 and TLR4 expression were relatively higher at the protein level. UC-MSCs expressed functional TLRs by nuclear factor-κB activation and cytokine expression assay. Poly-inosinic acid:cytidylic acid [Poly(I:C)] stimulation inhibited the proliferation of UC-MSCs, but the ligand of other TLRs had no significant effect. Poly(I:C) stimulation enhanced the adipogenic differentiation capability of UC-MSCs, but lipopolysaccharide inhibited the adipogenic differentiation. Poly(I:C) and CpG-oligonucleotide promoted the immunosuppressive potentiality of UC-MSCs, accompanied with the phosphorylation of interferon regulatory factor 3 (IRF3) and increased expression of indoleamine 2,3-dioxygenase and interferon β, whereas activation of other TLR ligands (synthetic analog fibroblast-stimulating lipopeptide-1 and lipopolysaccharide) failed to affect the immunoregulatory activity of UC-MSCs.ConclusionsTaken together, our data demonstrated that TLR activation influenced the function of UC-MSCs, which might have important implications in future efforts to explore the clinical potentials of UC-MSCs. 相似文献
83.
Eun-Young Won Mi-Kyung Yoon Sang-Woo Kim Youngae Jung Hyun-Whee Bae Daeyoup Lee Sung Goo Park Chul-Ho Lee Geum-Sook Hwang Seung-Wook Chi 《PloS one》2013,8(10)
Despite the numerous metabolic studies on obesity, gender bias in obesity has rarely been investigated. Here, we report the metabolomic analysis of obesity by using leptin-deficient ob/ob mice based on the gender. Metabolomic analyses of urine and serum from ob/ob mice compared with those from C57BL/6J lean mice, based on the 1H NMR spectroscopy in combination with multivariate statistical analysis, revealed clear metabolic differences between obese and lean mice. We also identified 48 urine and 22 serum metabolites that were statistically significantly altered in obese mice compared to lean controls. These metabolites are involved in amino acid metabolism (leucine, alanine, ariginine, lysine, and methionine), tricarbocylic acid cycle and glucose metabolism (pyruvate, citrate, glycolate, acetoacetate, and acetone), lipid metabolism (cholesterol and carnitine), creatine metabolism (creatine and creatinine), and gut-microbiome-derived metabolism (choline, TMAO, hippurate, p-cresol, isobutyrate, 2-hydroxyisobutyrate, methylamine, and trigonelline). Notably, our metabolomic studies showed distinct gender variations. The obese male mice metabolism was specifically associated with insulin signaling, whereas the obese female mice metabolism was associated with lipid metabolism. Taken together, our study identifies the biomarker signature for obesity in ob/ob mice and provides biochemical insights into the metabolic alteration in obesity based on gender. 相似文献
84.
Rajesh Mohandas Larysa Sautina Shiyu Li Xuerong Wen Tianyao Huo Eileen Handberg Yueh-Yun Chi C. Noel Bairey Merz Carl J. Pepine Mark S. Segal 《PloS one》2013,8(12)
Background
In women with ischemia and no obstructive coronary artery disease, the Women''s Ischemic Syndrome Evaluation (WISE) observed that microvascular coronary dysfunction (MCD) is the best independent predictor of adverse cardiovascular events. Since coronary microvascular tone is regulated in part by endothelium, we hypothesized that circulating endothelial cells (CEC), which reflect endothelial injury, and the number and function of bone-marrow derived angiogenic cells (BMDAC), which could help repair damaged endothelium, may serve as biomarkers for decreased coronary flow reserve (CFR) and MCD.Methods
We studied 32 women from the WISE cohort. CFR measurements in response to intracoronary adenosine were taken as an index of MCD. We enumerated BMDAC colonies and CEC in peripheral blood samples. BMDAC function was assessed by assay of migration of CD34+ cells toward SDF-1 and measurement of bioavailable nitric oxide (NO). These findings were compared with a healthy reference group and also entered into a multivariable model with CFR as the dependent variable.Results
Compared with a healthy reference group, women with MCD had lower numbers of BMDAC colonies [16 (0, 81) vs. 24 (14, 88); P = 0.01] and NO [936 (156, 1875) vs. 1168 (668, 1823); P = 0.02]. Multivariable regression analysis showed strong correlation of CFR to the combination of BMDAC colony count and CD34+ cell function (migration and NO) (R2 = 0.45; P<0.05).Conclusions
The BMDAC function and numbers of BMDAC colonies are decreased in symptomatic women with MCD and are independently associated with CFR. These circulating cells may provide mechanistic insights into MCD in women with ischemia. 相似文献85.
Jianjie Mi Alisa E. Shaw Chi W. Pak Keifer P. Walsh Laurie S. Minamide Barbara W. Bernstein Thomas B. Kuhn James R. Bamburg 《PloS one》2013,8(12)
Filament bundles (rods) of cofilin and actin (1:1) form in neurites of stressed neurons where they inhibit synaptic function. Live-cell imaging of rod formation is hampered by the fact that overexpression of a chimera of wild type cofilin with a fluorescent protein causes formation of spontaneous and persistent rods, which is exacerbated by the photostress of imaging. The study of rod induction in living cells calls for a rod reporter that does not cause spontaneous rods. From a study in which single cofilin surface residues were mutated, we identified a mutant, cofilinR21Q, which when fused with monomeric Red Fluorescent Protein (mRFP) and expressed several fold above endogenous cofilin, does not induce spontaneous rods even during the photostress of imaging. CofilinR21Q-mRFP only incorporates into rods when they form from endogenous proteins in stressed cells. In neurons, cofilinR21Q-mRFP reports on rods formed from endogenous cofilin and induced by all modes tested thus far. Rods have a half-life of 30–60 min upon removal of the inducer. Vesicle transport in neurites is arrested upon treatments that form rods and recovers as rods disappear. CofilinR21Q-mRFP is a genetically encoded rod reporter that is useful in live cell imaging studies of induced rod formation, including rod dynamics, and kinetics of rod elimination. 相似文献
86.
Ting Yan Guangdong Sun Weijie Chi Butong Li Haishun Wu 《Journal of molecular modeling》2013,19(9):3491-3499
A series of purine derivatives with nitramine groups are calculated by using density functional theory (DFT). The molecular theory density, heats of formation, bond dissociation energies and detonation performance are investigated at DFT-B3LYP/6-311G** level. The isodesmic reaction method is employed to calculate the HOFs of the energies obtained from electronic structure calculations. Results show that the position of nitramine groups can influence the values of HOFs. The bond dissociation energies and the impact sensitivity are analyzed to investigate the thermal stability of the purine derivatives. The calculated bond dissociation energies of ring-NHNO2 and NH-NO2 bond show that the NH-NO2 bond should be the trigger bond in pyrolysis processes. The H50 of most compounds are larger than that of CL-20 and RDX. 相似文献
87.
Jianmei Luo Meiling Chi Hongyu Wang Huanhuan He Minghua Zhou 《Bioprocess and biosystems engineering》2013,36(12):1889-1896
A convenient and promising alternative to surface modification of carbon mesh anode was fulfilled by electrochemical oxidation in the electrolyte of nitric acid or ammonium nitrate at ambient temperature. It was confirmed that such an anode modification method was low cost and effective not only in improving the efficiency of power generation in microbial fuel cells (MFCs) for synthetic wastewater treatment, but also helping to reduce the period for MFCs start-up. The MFCs with anode modification in electrolyte of nitric acid performed the best, achieving a Coulombic efficiency enhancement of 71 %. As characterized, the electrochemical modification resulted in the decrease of the anode potential and internal resistance but the increase of current response and nitrogen-containing and oxygen-containing functional groups on the carbon surface, which might contribute to the enhancement on the performances of MFCs. 相似文献
88.
89.
Yu-Jue Wang Wen Liu Chi Chen Li-Meng Yan Jun Song Kun-Yuan Guo Gang Wang Qing-Hong Wu Wei-Wang Gu 《PloS one》2013,8(3)
Background
The radiation-induced energy metabolism dysfunction related to injury and radiation doses is largely elusive. The purpose of this study is to investigate the early response of energy metabolism in small intestinal tissue and its correlation with pathologic lesion after total body X-ray irradiation (TBI) in Tibet minipigs.Methods and Results
30 Tibet minipigs were assigned into 6 groups including 5 experimental groups and one control group with 6 animals each group. The minipigs in these experimental groups were subjected to a TBI of 2, 5, 8, 11, and 14 Gy, respectively. Small intestine tissues were collected at 24 h following X-ray exposure and analyzed by histology and high performance liquid chromatography (HPLC). DNA contents in this tissue were also examined. Irradiation causes pathologic lesions and mitochondrial abnormalities. The Deoxyribonucleic acid (DNA) content-corrected and uncorrected adenosine-triphosphate (ATP) and total adenine nucleotides (TAN) were significantly reduced in a dose-dependent manner by 2–8 Gy exposure, and no further reduction was observed over 8 Gy.Conclusion
TBI induced injury is highly dependent on the irradiation dosage in small intestine and inversely correlates with the energy metabolism, with its reduction potentially indicating the severity of injury. 相似文献90.
Myeloperoxidase (MPO) functions as a key molecular component of the host defense system against diverse pathogens. We have previously reported that increased MPO levels and activity is a distinguishing feature of rotenone-exposed glial cells, and that either overactivation or deficiency of MPO leads to pathological conditions in the brain. Here, we provide that modulation of MPO levels in glia by resveratrol confers protective effects on rotenone-induced neurotoxicity. We show that resveratrol significantly reduced MPO levels but did not trigger abnormal nitric oxide (NO) production in microglia and astrocytes. Resveratrol-induced down-regulation of MPO, in the absence of an associated overproduction of NO, markedly attenuated rotenone-triggered inflammatory responses including phagocytic activity and reactive oxygen species production in primary microglia and astrocytes. In addition, impaired responses of primary mixed glia from Mpo
−/− mice to rotenone were relieved by treatment with resveratrol. We further show that rotenone-induced neuronal injury, particularly dopaminergic cell death, was attenuated by resveratrol in neuron-glia co-cultures, but not in neurons cultured alone. Similar regulatory effects of resveratrol on MPO levels were observed in microglia treated with MPP+, another Parkinson’s disease-linked neurotoxin, supporting the beneficial effects of resveratrol on the brain. Collectively, our findings provide that resveratrol influences glial responses to rotenone by regulating both MPO and NO, and thus protects against rotenone-induced neuronal injury. 相似文献