全文获取类型
收费全文 | 4581篇 |
免费 | 427篇 |
国内免费 | 252篇 |
专业分类
5260篇 |
出版年
2024年 | 6篇 |
2023年 | 51篇 |
2022年 | 130篇 |
2021年 | 222篇 |
2020年 | 147篇 |
2019年 | 206篇 |
2018年 | 211篇 |
2017年 | 141篇 |
2016年 | 186篇 |
2015年 | 295篇 |
2014年 | 300篇 |
2013年 | 377篇 |
2012年 | 378篇 |
2011年 | 357篇 |
2010年 | 216篇 |
2009年 | 182篇 |
2008年 | 249篇 |
2007年 | 212篇 |
2006年 | 170篇 |
2005年 | 174篇 |
2004年 | 118篇 |
2003年 | 124篇 |
2002年 | 98篇 |
2001年 | 98篇 |
2000年 | 74篇 |
1999年 | 81篇 |
1998年 | 60篇 |
1997年 | 45篇 |
1996年 | 57篇 |
1995年 | 54篇 |
1994年 | 31篇 |
1993年 | 33篇 |
1992年 | 33篇 |
1991年 | 28篇 |
1990年 | 20篇 |
1989年 | 21篇 |
1988年 | 13篇 |
1987年 | 16篇 |
1986年 | 8篇 |
1985年 | 9篇 |
1984年 | 9篇 |
1983年 | 5篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1980年 | 5篇 |
1979年 | 1篇 |
1978年 | 3篇 |
1976年 | 1篇 |
1974年 | 1篇 |
1959年 | 1篇 |
排序方式: 共有5260条查询结果,搜索用时 0 毫秒
961.
William S. Lagakos Xudong Guan Shiu-Ying Ho Luciana Rodriguez Sawicki Betina Corsico Sarala Kodukula Kaeko Murota Ruth E. Stark Judith Storch 《The Journal of biological chemistry》2013,288(27):19805-19815
Liver fatty acid-binding protein (LFABP; FABP1) is expressed both in liver and intestinal mucosa. Mice null for LFABP were recently shown to have altered metabolism of not only fatty acids but also monoacylglycerol, the two major products of dietary triacylglycerol hydrolysis (Lagakos, W. S., Gajda, A. M., Agellon, L., Binas, B., Choi, V., Mandap, B., Russnak, T., Zhou, Y. X., and Storch, J. (2011) Am. J. Physiol. Gastrointest. Liver Physiol. 300, G803–G814). Nevertheless, the binding and transport of monoacylglycerol (MG) by LFABP are uncertain, with conflicting reports in the literature as to whether this single chain amphiphile is in fact bound by LFABP. In the present studies, gel filtration chromatography of liver cytosol from LFABP−/− mice shows the absence of the low molecular weight peak of radiolabeled monoolein present in the fractions that contain LFABP in cytosol from wild type mice, indicating that LFABP binds sn-2 MG in vivo. Furthermore, solution-state NMR spectroscopy demonstrates two molecules of sn-2 monoolein bound in the LFABP binding pocket in positions similar to those found for oleate binding. Equilibrium binding affinities are ∼2-fold lower for MG compared with fatty acid. Finally, kinetic studies examining the transfer of a fluorescent MG analog show that the rate of transfer of MG is 7-fold faster from LFABP to phospholipid membranes than from membranes to membranes and occurs by an aqueous diffusion mechanism. These results provide strong support for monoacylglycerol as a physiological ligand for LFABP and further suggest that LFABP functions in the efficient intracellular transport of MG. 相似文献
962.
963.
Lei Peng-Cheng Takashi Yoshiike Hitoshi Yaguchi Hideoki Ogawa MD PhD 《Mycopathologia》1993,122(2):89-93
Defense mechanisms againstSporothrix schenckii were studied using mouse models. After an intracutaneous injection of the yeast form ofS. schenckii to the dorsal skin of the congenitally athymic nude and normal heterozygote littermate mice, nodules were formed. They regressed and disappeared in 10 weeks in the case of normal mice. On the other hand, nodules and then ulceration developed progressively in nude mice until all animals expired by dissemination of microorganisms at the 11th week of inoculation. Histopathologically the migrated cells were similar in both the normal and the nude mice, particularly during the early phase (within 24 h), with infiltration by PMNs being predominant. Fragmentation ofS. schenckii commenced early during the 12–24 h stage of inoculation in the normal mice, while such fragmentation was scarce in nude mice even though numerous PMNs accumulated. Microscopic observations in the early stages (within 24 h of inoculation) suggested that the lack of killing activity by PMNs in nude mice contributes more to the impaired defense than the lack of macrophage activation by T-cells. 相似文献
964.
Jenifer L. Smith Kassandra I. Rossiter Christopher M. Semko Ying-Zi Xu David A. Quincy Jacek Jagodzinski Michael S. Dappen Andrei W. Konradi Christopher Vandevert Caroline Garrido Wenxian Mao F. Bong San Pablo Brian Wipke Lilibeth Dofiles Angie Wadsworth Eric Peterson Carlos Lorenzana Stellanie Simmonds Ted A. Yednock 《Bioorganic & medicinal chemistry letters》2013,23(14):4117-4119
Mitsunobu reactions were employed to link t-butyl esters of α4 integrin inhibitors at each of the termini of a three-arm, 40 kDa, branched PEG. Cleavage of the t-butyl esters using HCO2H provided easily isolated PEG derivatives, which are potent α4 integrin inhibitors, and which achieve sustained levels and bioactivity in vivo, following subcutaneous administration to rats. 相似文献
965.
Comparative performance of different scale‐down simulators of substrate gradients in Penicillium chrysogenum cultures: the need of a biological systems response analysis 下载免费PDF全文
966.
967.
Predicted avian responses to bioenergy development scenarios in an intensive agricultural landscape 下载免费PDF全文
Daniel R. Uden Craig R. Allen Rob B. Mitchell Tim D. McCoy Qingfeng Guan 《Global Change Biology Bioenergy》2015,7(4):717-726
Conversion of native prairie to agriculture has increased food and bioenergy production but decreased wildlife habitat. However, enrollment of highly erodible cropland in conservation programs has compensated for some grassland loss. In the future, climate change and production of second-generation perennial biofuel crops could further transform agricultural landscapes and increase or decrease grassland area. Switchgrass (Panicum virgatum) is an alternative biofuel feedstock that may be economically and environmentally superior to maize (Zea mays) grain for ethanol production on marginally productive lands. Switchgrass could benefit farmers economically and increase grassland area, but there is uncertainty as to how conversions between rowcrops, switchgrass monocultures and conservation grasslands might occur and affect wildlife. To explore potential impacts on grassland birds, we developed four agricultural land-use change scenarios for an intensively cultivated landscape, each driven by potential future climatic changes and ensuing irrigation limitations, ethanol demand, commodity prices, and continuation of a conservation program. For each scenario, we calculated changes in area for landcover classes and predicted changes in grassland bird abundances. Overall, birds responded positively to the replacement of rowcrops with switchgrass and negatively to the conversion of conservation grasslands to switchgrass or rowcrops. Landscape context and interactions between climate, crop water use, and irrigation availability could influence future land-use, and subsequently, avian habitat quality and quantity. Switchgrass is likely to provide higher quality avian habitat than rowcrops but lower quality habitat than conservation grasslands, and therefore, may most benefit birds in heavily cultivated, irrigation dependent landscapes under warmer and drier conditions, where economic profitability may also encourage conversions to drought tolerant bioenergy feedstocks. 相似文献
968.
Gax suppresses chemerin/CMKLR1‐induced preadipocyte biofunctions through the inhibition of Akt/mTOR and ERK signaling pathways 下载免费PDF全文
Yunqi Jiang MD Ping Liu MD PhD Wenlin Jiao MD Juan Meng MD Jinbo Feng MD 《Journal of cellular physiology》2018,233(1):572-586
Adipose tissue is closely associated with angiogenesis and vascular remodeling. Chemerin is involved in inflammatory reaction and vascular dysfunction. However, the mechanisms of chemerin participating in vascular remodeling and whether Growth arrest‐specific homeobox (Gax) can effectively intervene it remain obscured. Here, 3T3‐F442A preadipocytes were cultured, injected into athymic mice to model fat pads, and treated respectively with Ad‐chemerin, Ad‐Gax, or specific inhibitors in vitro and in vivo. MTT, flow cytometry, Western blotting, and imunohisto(cyto)‐chemistry analyses showed that chemerin enhanced the expression of FABP4 and VEGF, activated Akt/mTOR and ERK pathways, increased the cell percent of S phase, decreased the percent of G0‐G1 phase and apoptotic cells, and augmented neovascular density in fat pads. Inversely, Gax suppressed the expression of these adipogenic and vasifactive markers and these signaling proteins, decreased the percent of S phase cells, and increased those of G0‐G1 phase and apoptotic cells, and reduced the neovascular density. Our results indicate that chemerin‐CMKLR1 activates Akt/mTOR and ERK pathways and facilitates preadipocyte proliferation, adipogenesis, and angiogenesis. Contrarily, Gax weakens the effect of chemerin on preadipocyte biofunctions. 相似文献
969.
A cancer microenvironment generates strong hydrogen bond network system by the positive feedback loops supporting cancer complexity and robustness. Such network functions through the AKT locus generating high entropic energy supporting cancer metastatic robustness. Charged lepton particle muon follows the rule of Bragg effect during a collision with hydrogen network in cancer cells. Muon beam dismantles hydrogen bond network in cancer by the muon-catalyzed fusion, leading to apoptosis of cancer cells. Muon induces cumulative energy appearance on the hydrogen bond network in a cancer cell with its fast decay to an electron and two neutrinos. Thus, muon beam, muonic atom, muon neutrino shower, and electrons simultaneously cause fast neutralization of the AKT hydrogen bond network by the conversion of hydrogen into deuterium or helium, inactivating the hydrogen bond networks and inducing failure of cancer complexity and robustness with the disappearance of a malignant phenotype. 相似文献
970.
Garima Singhal ffolliott Martin Fisher Melissa J. Chee Tze Guan Tan Abdelfattah El Ouaamari Andrew C. Adams Robert Najarian Rohit N. Kulkarni Christophe Benoist Jeffrey S. Flier Eleftheria Maratos-Flier 《PloS one》2016,11(2)
Fibroblast growth factor 21 (FGF21) is an important endocrine metabolic regulator expressed in multiple tissues including liver and adipose tissue. Although highest levels of expression are in pancreas, little is known about the function of FGF21 in this tissue. In order to understand the physiology of FGF21 in the pancreas, we analyzed its expression and regulation in both acinar and islet tissues. We found that acinar tissue express 20-fold higher levels than that observed in islets. We also observed that pancreatic FGF21 is nutritionally regulated; a marked reduction in FGF21 expression was noted with fasting while obesity is associated with 3–4 fold higher expression. Acinar and islet cells are targets of FGF21, which when systemically administered, leads to phosphorylation of the downstream target ERK 1/2 in about half of acinar cells and a small subset of islet cells. Chronic, systemic FGF21 infusion down-regulates its own expression in the pancreas. Mice lacking FGF21 develop significant islet hyperplasia and periductal lymphocytic inflammation when fed with a high fat obesogenic diet. Inflammatory infiltrates consist of TCRb+ Thy1+ T lymphocytes with increased levels of Foxp3+ regulatory T cells. Increased levels of inflammatory cells were coupled with elevated expression of cytokines such as TNFα, IFNγ and IL1β. We conclude that FGF21 acts to limit islet hyperplasia and may also prevent pancreatic inflammation. 相似文献