全文获取类型
收费全文 | 5076篇 |
免费 | 489篇 |
国内免费 | 1篇 |
出版年
2022年 | 25篇 |
2021年 | 53篇 |
2020年 | 35篇 |
2019年 | 44篇 |
2018年 | 41篇 |
2017年 | 47篇 |
2016年 | 98篇 |
2015年 | 169篇 |
2014年 | 165篇 |
2013年 | 239篇 |
2012年 | 312篇 |
2011年 | 354篇 |
2010年 | 218篇 |
2009年 | 196篇 |
2008年 | 274篇 |
2007年 | 331篇 |
2006年 | 295篇 |
2005年 | 318篇 |
2004年 | 319篇 |
2003年 | 292篇 |
2002年 | 322篇 |
2001年 | 63篇 |
2000年 | 45篇 |
1999年 | 85篇 |
1998年 | 81篇 |
1997年 | 68篇 |
1996年 | 60篇 |
1995年 | 52篇 |
1994年 | 59篇 |
1993年 | 57篇 |
1992年 | 51篇 |
1991年 | 39篇 |
1990年 | 42篇 |
1989年 | 44篇 |
1988年 | 40篇 |
1987年 | 41篇 |
1986年 | 36篇 |
1985年 | 33篇 |
1984年 | 49篇 |
1983年 | 39篇 |
1982年 | 43篇 |
1981年 | 44篇 |
1980年 | 34篇 |
1979年 | 29篇 |
1978年 | 34篇 |
1977年 | 36篇 |
1976年 | 36篇 |
1974年 | 22篇 |
1973年 | 38篇 |
1972年 | 23篇 |
排序方式: 共有5566条查询结果,搜索用时 484 毫秒
161.
Damon A. Lowes Carol Wallace Michael P. Murphy Nigel R. Webster 《Free radical research》2013,47(4):323-328
Tendinitis and tendon rupture during treatment with fluoroquinolone antibiotics is thought to be mediated via oxidative stress. This study investigated whether ciprofloxacin and moxifloxacin cause oxidative stress and mitochondrial damage in cultured normal human Achilles’ tendon cells and whether an antioxidant targeted to mitochondria (MitoQ) would protect against such damage better than a non-mitochondria targeted antioxidant. Human tendon cells from normal Achilles’ tendons were exposed to 0–0.3 mm antibiotic for 24 h and 7 days in the presence of 1 µm MitoQ or an untargeted form, idebenone. Both moxifloxacin and ciprofloxacin resulted in up to a 3-fold increase in the rate of oxidation of dichlorodihydrofluorescein, a marker of general oxidative stress in tenocytes (p<0.0001) and loss of mitochondrial membrane permeability (p<0.001). In cells treated with MitoQ the oxidative stress was less and mitochondrial membrane potential was maintained. Mitochondrial damage to tenocytes during fluoroquinolone treatment may be involved in tendinitis and tendon rupture. 相似文献
162.
Carol A. Belzer Louisa B. Tabatabai Glynn H. Frank 《Preparative biochemistry & biotechnology》2013,43(4):343-355
ABSTRACT Pasteurella haemolytica serovar A1 is the causative agent of acute fibrinohemorrahgic pneumonia also known as shipping fever. Many pathogens, including P. haemolytica, survive in their respective hosts through the up-regulation of an iron acquisition system. In this study we identified, purified and characterized a 35-kDa periplasmic iron-regulated protein. The N-terminal sequence of the iron-regulated protein ANEVNVYSYRQP YLIEPMLK was identical to the deduced amino acid sequence of the ferric binding protein, FbpA, of P. haemolytica. Growth of P. haemolytica in a synthetic medium (RPMI-1640), without iron and supplemented with 50 μM 2,2' dipyridyl, facilitated the expression, isolation and purification of the native P. haemolytica FbpA. 相似文献
163.
Robert Vince Mei Hua Carol A. Caperelli 《Nucleosides, nucleotides & nucleic acids》2013,32(11-12):1711-1718
Abstract Analogs of intermediates in the de novo purine nucleotide biosynthetic pathway were synthesized to study the binding requirements of the corresponding enzymes. Because of the instability of the natural stubstrates, such as phosphoribosylamine, the use of the structurally stable phosphonate moiety and the carbocyclic ribose yields ideal analogs for these studies. In addition, these analogs can act as potential inhibitors of the de novo pathway leading to the design of anticancer agents. Enzyme studies with GAR synthetase and GAR transformylase reveal that the title compounds can act as substrates or inhibitors of the de novo enzymes. 相似文献
164.
Abstract 5-Substituted 6-azauracils were alkylated with (2-acetoxyethoxy)methyl bromide to give protected acyclic nucleosides which were deprotected to afford acyclonucleosides of 5-substituted 6-azauracils. Their structures have been established by the UV and 1H-NMR spectra and by elemental analysis. 相似文献
165.
Jinqian Liu Alan Skradis Carol Kolar Jeff Kolath James Anderson Terrence Lawson 《Nucleosides, nucleotides & nucleic acids》2013,32(8):1789-1802
Abstract The efficacy of treatment with 5-Fluorouracil (5-FU) is limited, in part, by its inefficient conversion to 5-Fluoro-2′-deoxyuridine-5-O-monophosphate (FdUMP). We present data indicating that FdUMP[10], designed as a pro-drug for intracellular release of FdUMP, is cytotoxic as a consequence of uptake of the multimeric form. FdUMP[10] is stable in cell culture medium, with more than one-half of the material persisting as multimers of at least six nucleotides after a 48 h incubation at 37°C. FdUMP[10] is more than 400 times more cytotoxic than 5-FU towards human colorectal tumor cells (H630). FdUMP[10] also has decreased toxicity in vivo, with doses as high as 200 mg/kg/day (qdx3) administered to Balb/c mice without morbidity, compared to a maximum tolerated dose of 45 mg/kg/day for 5-FU using the same protocol. FdUMP[10] shows reduced sensitivity to OPRTase-and TK-mediated drug resistance, relative to 5-FU and FdU, respectively, and is much more cytotoxic than 5-FU towards cells that overexpress thymidylate synthase. Thus, FdUMP[10] is less susceptible to resistance mechanisms that limit the clinical utility of 5-FU. The increased cytotoxicity, decreased toxicity in vivo, and reduced sensitivity to drug resistance of FdUMP[10], relative to 5-FU, indicates multimeric FdUMP is potentially valuable as an antineoplastic agent, either as a single agent, or in combination with 5-FU. 相似文献
166.
Vijaya L. Damaraju Delores Mowles Sylvia Yao Amy Ng James D. Young Carol E. Cass 《Nucleosides, nucleotides & nucleic acids》2013,32(3):236-255
The nucleoside analogs 5-azacytidine (azacitidine) and 5-aza-2′-deoxycytidine (decitabine) are active against acute myeloid leukemia and myelodysplastic syndromes. Cellular transport across membranes is crucial for uptake of these highly polar hydrophilic molecules. We assessed the ability of azacitidine, decitabine, and, for comparison, gemcitabine, to interact with human nucleoside transporters (hNTs) in Saccharomyces cerevisiae cells (hENT1/2, hCNT1/2/3) or Xenopus laevis oocytes (hENT3/4). All three drugs inhibited hCNT1/3 potently (K i values, 3–26 μM), hENT1/2 and hCNT2 weakly (K i values, 0.5–3.1 mM), and hENT3/4 poorly if at all. Rates of transport of [3H]gemcitabine, [14C]azacitidine, and [3H]decitabine observed in Xenopus oocytes expressing individual recombinant hNTs differed substantially. Cytotoxicity of azacitidine and decitabine was assessed in hNT-expressing or hNT-deficient cultured human cell lines in the absence or presence of transport inhibitors where available. The rank order of cytotoxic sensitivities (IC 50 values, μM) conferred by hNTs were hCNT1 (0.1) > hENT1 (0.3) ? hCNT2 (8.3), hENT2 (9.0) for azacitidine and hENT1 (0.3) > hCNT1 (0.8) ? hENT2, hCNT2 (>100) for decitabine. Protection against cytotoxicity was observed for both drugs in the presence of inhibitors of nucleoside transport, thus suggesting the importance of hNTs in manifestation of toxicity. In summary, all seven hNTs transported azacitidine, with hCNT3 showing the highest rates, whereas hENT1 and hENT2 showed modest transport and hCNT1 and hCNT3 poor transport of decitabine. Our results show for the first time that azacitidine and decitabine exhibit different human nucleoside transportability profiles and their cytotoxicities are dependent on the presence of hNTs, which could serve as potential biomarkers of clinical response. 相似文献
167.
168.
169.
Chun-Yip Yeung Annette Wai-Kwan Tso Aimin Xu Yu Wang Yu-Cho Woo Tai-Hing Lam Su-Vui Lo Carol Ho-Yee Fong Nelson Ming-Sang Wat Jean Woo Bernard Man-Yung Cheung Karen Siu-Ling Lam 《PloS one》2013,8(10)
Background
Cytokines released from adipose tissues induce chronic low-grade inflammation, which may enhance cancer development. We investigated whether indices of obesity and circulating adipokine levels could predict incident cancer risk.Materials and Methods
This longitudinal community-based study included subjects from the Hong Kong Cardiovascular Risk Factors Prevalence Study (CRISPS) study commenced in 1995-1996 (CRISP-1) with baseline assessments including indices of obesity. Subjects were reassessed in 2000-2004 (CRISPS-2) with measurement of serum levels of adipokines including interleukin-6 (IL-6), soluble tumor necrosis factor receptor 2 (sTNFR2; as a surrogate marker of tumor necrosis factor-α activity), leptin, lipocalin 2, adiponectin and adipocyte-fatty acid binding protein (A-FABP). Incident cancer cases were identified up to 31 December 2011.Results
205 of 2893 subjects recruited at CRISPS-1 had developed incident cancers. More of the subjects who developed cancers were obese (22.1 vs 16.1%) or had central obesity (36.6 vs 24.5%) according to Asian cut-offs. Waist circumference (adjusted HR 1.02 [1.00-1.03] per cm; p=0.013), but not body mass index (adjusted HR 1.04 [1.00-1.08] per kg/m2; p=0.063), was a significant independent predictor for incident cancers after adjustment for age, sex and smoking status. 99 of 1899 subjects reassessed at CRISPS-2 had developed cancers. Subjects who developed cancers had significantly higher level of hsCRP, IL-6, sTNFR2 and lipocalin 2. After adjustment for conventional risk factors, only IL-6 (HR 1.51, 95% CI 1.18-1.95) and sTNFR2 (HR 3.27, 95%CI 1.65-6.47) predicted cancer development.Conclusions
Our data supported the increased risk of malignancy by chronic low grade inflammation related to central obesity. 相似文献170.
Carly Rich Marco Geraci Lucy Griffiths Francesco Sera Carol Dezateux Mario Cortina-Borja 《PloS one》2013,8(6)