全文获取类型
收费全文 | 6826篇 |
免费 | 618篇 |
国内免费 | 4篇 |
专业分类
7448篇 |
出版年
2023年 | 17篇 |
2022年 | 74篇 |
2021年 | 123篇 |
2020年 | 94篇 |
2019年 | 126篇 |
2018年 | 198篇 |
2017年 | 165篇 |
2016年 | 254篇 |
2015年 | 361篇 |
2014年 | 452篇 |
2013年 | 455篇 |
2012年 | 657篇 |
2011年 | 547篇 |
2010年 | 386篇 |
2009年 | 326篇 |
2008年 | 441篇 |
2007年 | 439篇 |
2006年 | 412篇 |
2005年 | 323篇 |
2004年 | 308篇 |
2003年 | 283篇 |
2002年 | 197篇 |
2001年 | 121篇 |
2000年 | 101篇 |
1999年 | 78篇 |
1998年 | 50篇 |
1997年 | 38篇 |
1996年 | 29篇 |
1995年 | 25篇 |
1994年 | 24篇 |
1993年 | 9篇 |
1992年 | 32篇 |
1991年 | 26篇 |
1990年 | 28篇 |
1989年 | 23篇 |
1988年 | 29篇 |
1987年 | 16篇 |
1986年 | 19篇 |
1985年 | 14篇 |
1984年 | 19篇 |
1983年 | 15篇 |
1982年 | 12篇 |
1981年 | 18篇 |
1980年 | 8篇 |
1979年 | 6篇 |
1978年 | 7篇 |
1977年 | 5篇 |
1976年 | 5篇 |
1973年 | 6篇 |
1972年 | 14篇 |
排序方式: 共有7448条查询结果,搜索用时 15 毫秒
21.
Sunkyung Lee Kyu Yang Yi Sung Jun Youn Byung Ho Lee Sung-eun Yoo 《Bioorganic & medicinal chemistry letters》2009,19(5):1329-1331
A series of (2-aryl-5-methylimidazol-4-ylcarbonyl)guanidines and (2-aryl-5-methyloxazol-4-ylcarbonyl)guanidines were synthesized and evaluated as NHE-1 inhibitors. The structure–activity relationships well matched those of furan derivatives, which were previously investigated. The (2,5-disubstituted)phenyl compounds showed better activities than the other analogues in both imidazole and oxazole compounds. Especially, 2-(2,5-dichlorophenyl)imidazole 52, and 2-(2-methoxy-5-chlorophenyl)imidazole 54 compounds exhibited potent cardioprotective efficacy both in vitro and in vivo as well as high NHE-1 inhibitory activities. 相似文献
22.
A hybrid model for erythrocyte membrane: a single unit of protein network coupled with lipid bilayer 下载免费PDF全文
To investigate the nanomechanics of the erythrocyte membrane we developed a hybrid model that couples the actin-spectrin network to the lipid bilayer. This model features a Fourier space Brownian dynamics model of the bilayer, a Brownian dynamics model of the actin protofilament, and a modified wormlike-chain model of the spectrin (including a cable-dynamics model to predict the oscillation in tension). This model enables us to predict the nanomechanics of single or multiple units of the protein network, the lipid bilayer, and the effect of their interactions. The present work is focused on the attitude of the actin protofilament at the equilibrium states coupled with the elevations of the lipid bilayer through their primary linkage at the suspension complex in deformations. Two different actin-spectrin junctions are considered at the junctional complex. With a point-attachment junction, large pitch angles and bifurcation of yaw angles are predicted. Thermal fluctuations at bifurcation may lead to mode-switching, which may affect the network and the physiological performance of the membrane. In contrast, with a wrap-around junction, pitch angles remain small, and the occurrence of bifurcation is greatly reduced. These simulations suggest the importance of three-dimensional molecular junctions and the lipid bilayer/protein network coupling on cell membrane mechanics. 相似文献
23.
Summary Deactivation ofCandida
rugosa lipase was found to be complex. Hydrophobic interaction induced by iso-octane influenced the initial phase of deactivation, and increased the turn-over rate of the intermediate in the transition phase. After urea-treatment the structure of the last phase was not further influenced by thermal treatment, whereas that of initial phase was more sensitive to temperature change. Charge interaction was important in maintaining the structure during the deactivation, and especially anion charge might be a major factor. 相似文献
24.
Lithium‐Ion Batteries: All‐Nanomat Lithium‐Ion Batteries: A New Cell Architecture Platform for Ultrahigh Energy Density and Mechanical Flexibility (Adv. Energy Mater. 22/2017) 下载免费PDF全文
25.
Noh HL Okajima K Molkentin JD Homma S Homma S Goldberg IJ 《American journal of physiology. Endocrinology and metabolism》2006,291(4):E755-E760
The most energy-requiring organ in the body, the cardiac muscle, relies primarily on lipoprotein-derived fatty acids. Prenatal loss of cardiac lipoprotein lipase (LPL) leads to hypertriglyceridemia, but no cardiac dysfunction, in young mice. Cardiac specific loss of LPL in 8-wk-old mice was produced by a 2-wk tamoxifen treatment of MerCreMer (MCM)/Lpl(flox/flox) mice. LPL gene deletion was confirmed by PCR analysis, and LPL mRNA expression was reduced by approximately 70%. One week after tamoxifen was completed, triglyceride was increased with LPL deletion, 162 +/- 53 vs. 91 +/- 21 mg/dl, P < 0.01. Tamoxifen treatment of Lpl(flox/flox) mice did not cause a significant increase in triglyceride levels. Four weeks after tamoxifen, MCM/Lpl(flox/flox) mice had triglyceride levels of 190 +/- 27 mg/dl, similar to those of mice with prenatal LPL deletion. One week after the tamoxifen, MCM/Lpl(flox/flox), but not Lpl(flox/flox), mice had decreases in carnitine palmitoyl transferase I mRNA (18%) and pyruvate dehydrogenase kinase 4 mRNA (38%). These changes in gene expression became more robust with time. Acute loss of LPL decreased ejection fraction and increased mRNA levels for atrial natriuretic factor. Our studies show that acute loss of LPL can be produced and leads to rapid alteration in gene expression and cardiac dysfunction. 相似文献
26.
Han SN Leka LS Lichtenstein AH Ausman LM Meydani SN 《Journal of lipid research》2003,44(12):2304-2310
Hypercholesterolemia is a risk factor for coronary heart disease (CHD) and also could contribute to impaired immune response. The National Cholesterol Education Program Expert Panel recommends a therapeutic lifestyle change (TLC) diet to reduce the risk for CHD. We investigated the effects of changing from a high-fat Western diet to a low-fat diet in accordance with a TLC diet on immune functions of older adults with hypercholesterolemia to determine whether improving the lipid profile via dietary intervention would have beneficial effects on immune functions. In a double-blind study, 18 subjects consumed both a Western diet (38% fat) and a TLC diet (28% fat) for 32 days in a randomized order. Measures of cellular immune responses, including delayed-type hypersensitivity (DTH) response, in vitro lymphocyte proliferation, and interleukin (IL)-2 production, and production of proinflammatory mediators, including tumor necrosis factor-alpha, IL-6, IL-1beta, and prostaglandin E2, were determined. DTH response and lymphocyte proliferative response increased significantly (29% and 27%, respectively) after consumption of a TLC diet. Our results indicate that consumption of a TLC diet enhances T cell-mediated immune functions in older adults with elevated cholesterol level. This might be a clinically important benefit, considering the decline of T cell-mediated immune functions with aging and evidence of impaired immune function associated with hypercholesterolemia. 相似文献
27.
28.
Song MS Moon HJ Kwon HI Pascua PN Lee JH Baek YH Woo KJ Choi J Lee S Yoo H Oh I Yoon Y Rho JB Sung MH Hong SP Kim CJ Choi YK 《Journal of microbiology (Seoul, Korea)》2012,50(3):478-488
The threat of a highly pathogenic avian influenza (HPAI) H5N1 virus causing the next pandemic remains a major concern. In this study, we evaluated the immunogenicity and efficacy of an inactivated whole-virus H5N1 pre-pandemic vaccine (MG1109) formulated by Green Cross Co., Ltd containing the hemagglutinin (HA) and neuraminidase (NA) genes of the clade 1 A/Vietnam/1194/04 virus in the backbone of A/Puerto Rico/8/34 (RgVietNam/04xPR8/34). Administration of the MG1109 vaccine (2-doses) in mice and ferrets elicited high HI and SN titers in a dose-dependent manner against the homologous (RgVietNam/04xPR8/34) and various heterologous H5N1 strains, (RgKor/W149/06xPR8/34, RgCambodia/04xPR8/34, RgGuangxi/05xPR8/34), including a heterosubtypic H5N2 (A/Aquatic bird/orea/W81/05) virus. However, efficient cross-reactivity was not observed against heterosubtypic H9N2 (A/Ck/Korea/H0802/08) and H1N1 (PR/8/34) viruses. Mice immunized with 1.9 μg HA/dose of MG1109 were completely protected from lethal challenge with heterologous wild-type HPAI H5N1 A/EM/Korea/W149/06 (clade 2.2) and mouse-adapted H5N2 viruses. Furthermore, ferrets administered at least 3.8 μg HA/dose efficiently suppressed virus growth in the upper respiratory tract and lungs. Vaccinated mice and ferrets also demonstrated attenuation of clinical disease signs and limited virus spread to other organs. Thus, this vaccine provided immunogenic responses in mouse and ferret models even against challenge with heterologous HPAI H5N1 and H5N2 viruses. Since the specific strain of HPAI H5N1 virus that would potentially cause the next outbreak is unknown, pre-pandemic vaccine preparation that could provide cross-protection against various H5 strains could be a useful approach in the selection of promising candidate vaccines in the future. 相似文献
29.
To survive in a subzero environment, polar organisms produce ice-binding proteins (IBPs). These IBPs prevent the formation of large intracellular ice crystals, which may be fatal to the organism. Recently, a recombinant FfIBP (an IBP from Flavobacterium frigoris PS1) was cloned and produced in Pichia pastoris using fed-batch fermentation with methanol feeding. In this study, we demonstrate that FfIBP produced by P. pastoris has a glycosylation site, which diminishes the thermal hysteresis activity of FfIBP. The FfIBP expressed by P. pastoris exhibited a doublet on SDS-PAGE. The results of a glycosidase reaction suggested that FfIBP possesses complex N-linked oligosaccharides. These results indicate that the residues of the glycosylated site could disturb the binding of FfIBP to ice molecules. The findings of this study could be utilized to produce highly active antifreeze proteins on a large scale. 相似文献
30.
To investigate the effect of human pyruvate carboxylase (hPC) on lactate formation in Chinese hamster ovary (CHO) cell lines,
FLAG-tagged hPC was introduced into a dihydrofolate-deficient CHO cell line (DG44). Three clones expressing high levels of
hPC, determined by Western blotting using an anti-FLAG monoclonal antibody, and a control cell line were established. Immunocytochemistry
revealed that a substantial amount of expressed hPC protein was localized in the mitochondria of the cells. hPC expression
did not impair cell proliferation. Rather, it improved cell viability at the end of adherent batch cultures with the serum-containing
medium probably because of reduced lactate formation. Compared with control cells, specific lactate production rate of the
three clones was decreased by 21–39%, which was because of a decreased specific glucose uptake rate and yield of lactate from
glucose. Reduced lactate formation by hPC expression was also observed in suspension fed-batch cultures using a serum-free
medium. Taken together, these results demonstrate that through the expression of the hPC enzyme, lactate formation in CHO
cell culture can be efficiently reduced. 相似文献