全文获取类型
收费全文 | 10537篇 |
免费 | 751篇 |
国内免费 | 8篇 |
专业分类
11296篇 |
出版年
2024年 | 14篇 |
2023年 | 45篇 |
2022年 | 149篇 |
2021年 | 232篇 |
2020年 | 170篇 |
2019年 | 205篇 |
2018年 | 321篇 |
2017年 | 300篇 |
2016年 | 453篇 |
2015年 | 681篇 |
2014年 | 745篇 |
2013年 | 809篇 |
2012年 | 1007篇 |
2011年 | 951篇 |
2010年 | 590篇 |
2009年 | 505篇 |
2008年 | 705篇 |
2007年 | 653篇 |
2006年 | 548篇 |
2005年 | 477篇 |
2004年 | 423篇 |
2003年 | 386篇 |
2002年 | 301篇 |
2001年 | 128篇 |
2000年 | 118篇 |
1999年 | 96篇 |
1998年 | 51篇 |
1997年 | 45篇 |
1996年 | 25篇 |
1995年 | 28篇 |
1994年 | 14篇 |
1993年 | 13篇 |
1992年 | 14篇 |
1991年 | 17篇 |
1990年 | 7篇 |
1989年 | 11篇 |
1988年 | 9篇 |
1987年 | 4篇 |
1986年 | 4篇 |
1985年 | 10篇 |
1984年 | 8篇 |
1983年 | 3篇 |
1982年 | 4篇 |
1980年 | 3篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1972年 | 1篇 |
1971年 | 3篇 |
1969年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
41.
Because of the recent observation of the toxic side effects of Gd(III) based MRI contrast agents in patients with impaired renal function, there is strong interest on developing alternative contrast agents for MRI. In this study, macrocyclic Mn(II) chelates were conjugated to nanoglobular carriers, lysine dendrimers with a silsesquioxane core, to synthesize non-Gd(III) based MRI contrast agents. A generation 3 nanoglobular conjugate of Mn(II)-1,4,7-triaazacyclononane-1,4,7-triacetate-GA amide (G3-NOTA-Mn) was also synthesized and evaluated. The per ion T(1) and T(2) relaxivities of G2, G3, G4 nanoglobular Mn(II)-DOTA monoamide conjugates decreased with increasing generation of the carriers. The T(1) relaxivities of G2, G3, and G4 nanoglobular Mn(II)-DOTA conjugates were 3.3, 2.8, and 2.4 mM(-1) s(-1) per Mn(II) chelate at 3 T, respectively. The T(1) relaxivity of G3-NOTA-Mn was 3.80 mM(-1) s(-1) per Mn(II) chelate at 3 T. The nanoglobular macrocyclic Mn(II) chelate conjugates showed good in vivo stability and were readily excreted via renal filtration. The conjugates resulted in much less nonspecific liver enhancement than MnCl(2) and were effective for contrast-enhanced tumor imaging in nude mice bearing MDA-MB-231 breast tumor xenografts at a dose of 0.03 mmol Mn/kg. The nanoglobular macrocyclic Mn(II) chelate conjugates are promising nongadolinium based MRI contrast agents. 相似文献
42.
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
43.
44.
Jeon SB Jin F Kim JI Kim SH Suk K Chae SC Jun JE Park WH Kim IK 《Biochemical and biophysical research communications》2006,343(1):27-33
Agonist and depolarization-induced vascular smooth muscle contractions involve the activation of Rho-kinase pathway. However, there are no reports addressing the question whether this pathway is involved in NaF-induced vascular contractions. We hypothesized that Rho-kinase plays a role in vascular contraction evoked by sodium fluoride in rat aortae. In both physiological salt solution and calcium-free solution with 2 mM EGTA, cumulative addition of NaF increased vascular tension in concentration-dependent manners. Effects of Rho-kinase inhibitor (Y27632) on phosphorylation of myosin light chain (MLC20) and myosin targeting subunit (MYPT1(Thr696)) of myosin light chain phosphatase as well as NaF-induced contractions were determined using isolated tissue and the Western blot experiments. Y27632 inhibited NaF-induced contractions in a concentration-dependent manner. NaF increased phosphorylation of MLC20 and MYPT1(Thr696), which were also inhibited by Y27632. However, MLCK inhibitor (ML-7) or PKC inhibitor (Ro31-8220) did not inhibit the NaF-induced contraction. These results indicate that activation of Rho-kinase and the subsequent phosphorylation of MYPT1(Thr696) play important roles in NaF-induced contraction of rat aortae. 相似文献
45.
The amino‐terminal tail of Hxt11 confers membrane stability to the Hxt2 sugar transporter and improves xylose fermentation in the presence of acetic acid 下载免费PDF全文
Hyun Yong Shin Jeroen G. Nijland Paul P. de Waal Arnold J. M. Driessen 《Biotechnology and bioengineering》2017,114(9):1937-1945
Hxt2 is a glucose repressed, high affinity glucose transporter of the yeast Saccharomyces cerevisiae and is subjected to high glucose induced degradation. Hxt11 is a sugar transporter that is stably expressed at the membrane irrespective the sugar concentration. To transfer this property to Hxt2, the N‐terminal tail of Hxt2 was replaced by the corresponding region of Hxt11 yielding a chimeric Hxt11/2 transporter. This resulted in the stable expression of Hxt2 at the membrane and improved the growth on 8% d ‐glucose and 4% d ‐xylose. Mutation of N361 of Hxt11/2 into threonine reversed the specificity for d ‐xylose over d ‐glucose with high d ‐xylose transport rates. This mutant supported efficient sugar fermentation of both d ‐glucose and d ‐xylose at industrially relevant sugar concentrations even in the presence of the inhibitor acetic acid which is normally present in lignocellulosic hydrolysates. Biotechnol. Bioeng. 2017;114: 1937–1945. © 2017 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc. 相似文献
46.
47.
Jang Hye Jin Choi Ji Yeon Kim Kangjoon Yong Seung Hyun Kim Yeon Wook Kim Song Yee Kim Eun Young Jung Ji Ye Kang Young Ae Park Moo Suk Kim Young Sam Cho Young-Jae Lee Sang Hoon 《Respiratory research》2021,22(1):1-9
IL-35 subunit EBI3 is up-regulated in pulmonary fibrosis tissues. In this study, we investigated the pathological role of EBI3 in pulmonary fibrosis and dissected the underlying molecular mechanism. Bleomycin-induced pulmonary fibrosis mouse model was established, and samples were performed gene expression analyses through RNAseq, qRT-PCR and Western blot. Wild type and EBI3 knockout mice were exposed to bleomycin to investigate the pathological role of IL-35, via lung function and gene expression analyses. Primary lung epithelial cells were used to dissect the regulatory mechanism of EBI3 on STAT1/STAT4 and STAT3. IL-35 was elevated in both human and mouse with pulmonary fibrosis. EBI3 knockdown aggravated the symptoms of pulmonary fibrosis in mice. EBI3 deficiency enhanced the expressions of fibrotic and extracellular matrix-associated genes. Mechanistically, IL-35 activated STAT1 and STAT4, which in turn suppressed DNA enrichment of STAT3 and inhibited the fibrosis process. IL-35 might be one of the potential therapeutic targets for bleomycin-induced pulmonary fibrosis. 相似文献
48.
Daniel C. Ilut Alexander E. Lipka Namhee Jeong Dong Nyuk Bae Dong Hyun Kim Ji Hong Kim Neelam Redekar Kiwoung Yang Won Park Sung-Taeg Kang Namshin Kim Jung-Kyung Moon M. A. Saghai Maroof Michael A. Gore Soon-Chun Jeong 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2016,129(3):453-468
49.
Sphingosine-1-phosphate (S1P) is considered to be an important regulator of diverse biological processes acting as a natural ligand to EDG receptors. As a preliminary study to develop potent and selective agonist and antagonist for EDG receptors, we report synthesis of S1P stereoisomers and analogues and their binding affinities to EDG-1, -3, and -5. 相似文献
50.
Jeong HT Oowatari Y Abe M Tanaka K Matsuda H Kawamukai M 《Bioscience, biotechnology, and biochemistry》2004,68(7):1621-1626
The sexual differentiation of Schizosaccharomyces pombe is controlled by many cellular components which have not been fully characterized. We isolated a gene called msa2 as a multi-copy suppressor of a sporulation abnormal mutant (sam1). Msa2p is identical with Nrd1p which has been characterized as a factor that blocks the onset of sexual differentiation. The yeast two-hybrid system was used to identify Cpc2p, a fission yeast homolog of the RACK1 protein, that interacted with Msa2p/Nrd1p. We confirmed that Msa2p/Nrd1p interacted with Cpc2p in S. pombe cells. An epistatic analysis of msa2/nrd1 and cpc2 suggests that Msa2p/Nrd1p was an upstream regulator for Cpc2p. A localization analysis of Cpc2p and Msa2p/Nrd1p indicates that both proteins were predominantly localized in the cytoplasm. The interaction of negative regulator Msa2p/Nrd1p with positive regulator Cpc2p suggests a new regulatory circuit in the sexual differentiation of S. pombe. 相似文献