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991.
992.
Hung J Yang TL Urrutia TF Li R Perry CA Hata H Cogger EA Moriarty DJ Caudill MA 《The Journal of nutritional biochemistry》2006,17(11):728-734
The effectiveness of additional food folate in improving folate status in humans is uncertain particularly in people with the common genetic variant (677 C-->T) in the methylenetetrahydrofolate reductase (MTHFR) gene. To examine the effect of a doubling of food folate consumption on folate status response variables, women (n=32; 18-46 years) with the MTHFR 677 CC or TT genotype consumed either 400 (n=15; 7 CC and 8 TT) or 800 (n=17; 8 CC and 9 TT) microg/day of dietary folate equivalents (DFE) derived exclusively from naturally occurring food folate for 12 weeks. A repeated measures two-factor ANOVA was used to examine the effect of the dietary treatment, the MTHFR C677T genotype and their interactions on serum folate, RBC folate and plasma total homocysteine (tHcy) during the last 3 weeks of the study. Consumption of 800 microg DFE/day resulted in serum folate concentrations that were 67% (P=.005) higher than consumption of 400 microg DFE/day (18.6+/-2.9 vs. 31.0+/-2.7 nmol/L, respectively) and RBC folate concentrations that were 33% (P=.001) higher (1172+/-75 vs. 1559+/-70 nmol/L, respectively). Serum folate (P=.065) and RBC folate (P=.022) concentrations were lower and plasma tHcy was higher (P=.039) in women with the MTHFR 677 TT genotype relative to the CC genotype. However, no genotype by dietary treatment interaction was detected. These data suggest that a doubling of food folate intake will lead to marked improvements in folate status in women with the MTHFR 677 CC or TT genotype. 相似文献
993.
A novel approach for extracting living cells' genomic DNA materials utilizing functionalized magnetic particles (MPs) is reported in this investigation. This strategy is amenable to handle bio-samples in a miniaturized environment and it offers a possibility to separate and purify DNA from other cell lysate mixtures "on-chip", which is known to be a bottle-neck step in an integrated micro-total-analysis-system (muTAS). "Species-specific" genomic DNA of interest is captured by the MPs based on the hybridization interaction between the biotinylated probes modified MPs and a complementary region of the targeted genome. The genome DNA anchored on the particles can be separated from the rest of cellular mixtures by a simple buffer washing upon the exertion of external magnetic force. Surface modifications of MPs and hybridization conditions affecting the genome capturing efficiency are investigated. Extraction of genomic DNA from E. coli is demonstrated in a silicon/glass-based micro-reactor patterned with a platinum heater and sensors. On-chip extraction and manipulation of genomic DNAs illustrated in this study is a step forward toward a total integrated bioanalytical microsystem for crude cells/sample analysis. 相似文献
994.
Duncton MA Piatnitski EL Katoch-Rouse R Smith LM Kiselyov AS Milligan DL Balagtas C Wong WC Kawakami J Doody JF 《Bioorganic & medicinal chemistry letters》2006,16(6):1579-1581
A novel class of 1-(isoquinolin-5-yl)-4-arylamino-phthalazines is described as inhibitors of vascular endothelial growth factor receptor II (VEGFR-2). Many compounds display VEGFR-2 inhibitory activity with an IC(50) as low as 0.017 microM in an HTRF enzymatic assay. The compounds also inhibit VEGFR-1, a related tyrosine kinase. 相似文献
995.
Watkins WJ Chen JM Cho A Chong L Collins N Fardis M Huang W Hung M Kirschberg T Lee WA Liu X Thomas W Xu J Zeynalzadegan A Zhang J 《Bioorganic & medicinal chemistry letters》2006,16(13):3479-3483
The design, synthesis, and IMPDH inhibitory activity of a series of phosphonic acid-containing analogues of mycophenolic acid are described. 相似文献
996.
Weihong Pan Chuanhui Yu Hung Hsuchou Reas S. Khan Abba J. Kastin 《Journal of neurochemistry》2009,111(3):819-827
The blood-brain barrier is a gatekeeper and modulatory interface for the CNS. Cerebral endothelial cells are the major component of the blood-brain barrier, and they modify inflammatory signals from the circulation to the CNS by production and secretion of secondary substances. The inflammatory mediators induced by tumor necrosis factor α (TNF) were determined by microarray analysis of RBE4 cerebral endothelial cells, at 0, 6, 12, or 24 h after TNF treatment. Interleukin (IL)-15 and its receptors were among the most robustly up-regulated genes. This was confirmed by real-time RT-PCR and western blotting. The three subunits of the IL15 receptor complex (IL15Rα, IL2Rβ, and IL2Rγ) showed differential regulation by TNF in their time course and amplitude of increased expression. Consistent with increased expression of the specific high affinity receptor IL15Rα, TNF increased cellular uptake of 125 I-IL15 and enhanced the fluorescent intensity of Alexa568-IL15 in RBE4 cells. TNF treatment in mice also increased the level of expression of IL15 receptors in enriched cerebral microvessels. We conclude that the cerebral microvascular IL15 system is a novel inflammatory mediator that transduces the actions of TNF. 相似文献
997.
Su Duy Nguyen Nguyen Dang Hung Park Cheon-Ho Kim Mee Ree Sok Dai-Eun 《Biochimica et Biophysica Acta (BBA)/General Subjects》2009
Paraoxonase1 (PON1), one of HDL-associated antioxidant proteins, is known to lose its activity in vivo systems under oxidative stress. Here, we examined the effect of various oxidants on lactonase activity of PON1, and tried to protect the lactonase activity from oxidative inactivation. Among the oxidative systems tested, the ascorbate/Cu2+ system was the most potent in inactivating the lactonase activity of purified PON1; in contrast to a limited role of Fe2+, Cu2+ (0.05–1.0 µM) remarkably enhanced the inactivation of PON1 in the presence of ascorbate (0.02–0.1 mM). Moreover, Cu2+ alone inhibited the lactonase activity at concentrations as low as 1 µM. The ascorbate/Cu2+-mediated inactivation of PON1 lactonase activity was prevented by catalase, but not general hydroxyl radical scavengers, suggesting the implication of Cu2+-bound hydroxyl radicals in the oxidative inactivation. Compared to arylesterase activity, lactonase activity appears to be more sensitive to Cu2+-catalyzed oxidation. Separately, ascorbate/Cu2+-mediated inactivation of lactonase activity was prevented by oleic acid as well as phoshatidylcholine. Taken together, our data demonstrate that Cu2+-catalyzed oxidation may be a primary factor to cause the decrease of PON1 lactonase activity under oxidative stress and that lactonase activity of PON1 is most susceptible to ascorbate/Cu2+ among PON1 activities. In addition, we have showed that radical-induced inactivation of lactonase activity is prevented by some lipids. 相似文献
998.
Samir Amrane Rita Wan Lin Ang Zhong Ming Tan Chun Li Joefina Kim Cheow Lim Jocelyn Mei Wen Lim Kah Wai Lim Anh Tun Phan 《Nucleic acids research》2009,37(3):931-938
Recently, the human telomeric d[TAGGG(TTAGGG)3] sequence has been shown to form in K+ solution an intramolecular (3+1) G-quadruplex structure, whose G-tetrad core contains three strands oriented in one direction and the fourth in the opposite direction. Here we present a study on the structure of the Bombyx mori telomeric d[TAGG(TTAGG)3] sequence, which differs from the human counterpart only by one G deletion in each repeat. We found that this sequence adopted multiple G-quadruplex structures in K+ solution. We have favored a major G-quadruplex form by a judicious U-for-T substitution in the sequence and determined the folding topology of this form. We showed by NMR that this was a new chair-type intramolecular G-quadruplex which involved a two-layer antiparallel G-tetrad core and three edgewise loops. Our result highlights the effect of G-tract length on the folding topology of G-quadruplexes, but also poses the question of whether a similar chair-type G-quadruplex fold exists in the human telomeric sequences. 相似文献
999.
Sequence variant (CTAGGG)n in the human telomere favors a G-quadruplex structure containing a G·C·G·C tetrad
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Kah Wai Lim Patrizia Alberti Aurore Guédin Laurent Lacroix Jean-Fran?ois Riou Nicola J. Royle Jean-Louis Mergny Anh Tuan Phan 《Nucleic acids research》2009,37(18):6239-6248
Short contiguous arrays of variant CTAGGG repeats in the human telomere are unstable in the male germline and somatic cells, suggesting formation of unusual structures by this repeat type. Here, we report on the structure of an intramolecular G-quadruplex formed by DNA sequences containing four human telomeric variant CTAGGG repeats in potassium solution. Our results reveal a new robust antiparallel G-quadruplex fold involving two G-tetrads sandwiched between a G·C base pair and a G·C·G·C tetrad, which could represent a new platform for drug design targeted to human telomeric DNA. 相似文献
1000.
Tseng CW Trimble C Zeng Q Monie A Alvarez RD Huh WK Hoory T Wang MC Hung CF Wu TC 《Cancer immunology, immunotherapy : CII》2009,58(5):737-748
Current therapeutic approaches to treatment of patients with bulky cervical cancer are based on conventional in situ ablative
modalities including cisplatin-based chemotherapy and radiation therapy. The 5-year survival of patients with nonresectable
disease is dismal. Because over 99% of squamous cervical cancer is caused by persistent infection with an oncogenic strain
of human papillomavirus (HPV), particularly type 16 and viral oncoproteins E6 and E7 are functionally required for disease
initiation and persistence, HPV-targeted immune strategies present a compelling opportunity in which to demonstrate proof
of principle. Sublethal doses of radiation and chemotherapeutic agents have been shown to have synergistic effect in combination
with either vaccination against cancer-specific antigens, or with passive transfer of tumor-specific cytotoxic T lymphocytes
(CTLs). Here, we explored the combination of low-dose radiation therapy with DNA vaccination with calreticulin (CRT) linked
to the mutated form of HPV-16 E7 antigen (E7(detox)), CRT/E7(detox) in the treatment of E7-expressing TC-1 tumors. We observed
that TC-1 tumor-bearing mice treated with radiotherapy combined with CRT/E7(detox) DNA vaccination generated significant therapeutic
antitumor effects and the highest frequency of E7-specific CD8+ T cells in the tumors and spleens of treated mice. Furthermore, treatment with radiotherapy was shown to render the TC-1
tumor cells more susceptible to lysis by E7-specific CTLs. In addition, we observed that treatment with radiotherapy during
the second DNA vaccination generated the highest frequency of E7-specific CD8+ T cells in the tumors and spleens of TC-1 tumor-bearing mice. Finally, TC-1 tumor-bearing mice treated with the chemotherapy
in combination with radiation and CRT/E7(detox) DNA vaccination generate significantly enhanced therapeutic antitumor effects.
The clinical implications of the study are discussed.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献