全文获取类型
收费全文 | 4698篇 |
免费 | 453篇 |
国内免费 | 104篇 |
专业分类
5255篇 |
出版年
2022年 | 43篇 |
2021年 | 90篇 |
2020年 | 34篇 |
2019年 | 50篇 |
2018年 | 81篇 |
2017年 | 53篇 |
2016年 | 102篇 |
2015年 | 241篇 |
2014年 | 267篇 |
2013年 | 288篇 |
2012年 | 367篇 |
2011年 | 373篇 |
2010年 | 241篇 |
2009年 | 186篇 |
2008年 | 256篇 |
2007年 | 228篇 |
2006年 | 232篇 |
2005年 | 196篇 |
2004年 | 187篇 |
2003年 | 136篇 |
2002年 | 120篇 |
2001年 | 133篇 |
2000年 | 104篇 |
1999年 | 58篇 |
1998年 | 42篇 |
1997年 | 37篇 |
1996年 | 42篇 |
1995年 | 27篇 |
1994年 | 41篇 |
1993年 | 31篇 |
1992年 | 67篇 |
1991年 | 50篇 |
1990年 | 57篇 |
1989年 | 63篇 |
1988年 | 38篇 |
1987年 | 50篇 |
1986年 | 33篇 |
1985年 | 45篇 |
1984年 | 38篇 |
1983年 | 33篇 |
1982年 | 49篇 |
1980年 | 20篇 |
1979年 | 42篇 |
1978年 | 25篇 |
1977年 | 33篇 |
1976年 | 33篇 |
1975年 | 40篇 |
1974年 | 36篇 |
1973年 | 40篇 |
1971年 | 24篇 |
排序方式: 共有5255条查询结果,搜索用时 0 毫秒
121.
Induced pluripotent stem (iPS) cell research has been growing a new height throughout the world due to its potentialities in medical applications. We can explore several therapeutic applications through the iPS cell research. In this review, we have first discussed the development of iPS cells, reprogramming factors, and effectiveness of iPS cells. Then we have emphasized the potential applications of iPS cells in pharmaceutical and medical sectors, such as, study of cellular mechanisms for spectrum of disease entities, disease-specific iPS cell lines for drugs discovery and development, toxicological studies of drugs development, personalized medicine, and regenerative medicine. 相似文献
122.
Jing‐Yuan Chuang Wei‐Hung Yang Hsien‐Te Chen Chun‐Yin Huang Tzu‐Wei Tan Yuh‐Tzy Lin Chin‐Jung Hsu Yi‐Chin Fong Chih‐Hsin Tang 《Journal of cellular physiology》2009,220(2):418-426
CCL5 (previously called RANTES) is in the CC‐chemokine family and plays a crucial role in the migration and metastasis of human cancer cells. On the other hand, the effect of CCL5 is mediated via CCR receptor. RT‐PCR and flow cytometry studies demonstrated CCR5 but not CCR1 and CCR3 mRNA in oral cancer cell lines, especially higher in those with high invasiveness (SCC4) as compared with lower levels in HSC3 cells and SCC9 cells. Stimulation of oral cancer cells with CCL5 directly increased the migration and metalloproteinase‐9 (MMP‐9) production. MMP‐9 small interfering RNA inhibited the CCL5‐induced MMP‐9 expression and thereby significantly inhibited the CCL5‐induced cell migration. Activations of phospholipase C (PLC), protein kinase Cδ (PKCδ), and NF‐κB pathways after CCL5 treatment was demonstrated, and CCL5‐induced expression of MMP‐9 and migration activity was inhibited by the specific inhibitor of PLC, PKCδ, and NF‐κB cascades. In addition, migration‐prone sublines demonstrate that cells with increasing migration ability had more expression of MMP‐9, CCL5, and CCR5. Taken together, these results indicate that CCL5/CCR5 axis enhanced migration of oral cancer cells through the increase of MMP‐9 production. J. Cell. Physiol. 220: 418–426, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
123.
Self-assembly reaction of Cd(ClO4)2 · 6H2O with Norfloxacin (H-Norf) affords a novel 2D rectangular grid framework [Cd(Norf)(ClO4)(H2O)] (1) with strong blue luminescent emission (λem=425 nm), while Norf− acts as a tetradentate bridging linker to connect three Cd centers and ClO4 − completes Cd center octahedron coordination geometry. The compound 1 has crystallographic data of triclinic, space group , a=9.4577(1) Å, b=9.5012(2) Å, c=12.2805(1) Å, V=3624.4(3) Å3, Z=2. 相似文献
124.
M Jadot L Lin D E Sleat I Sohar M S Hsu J Pintar F Dubois S Wattiaux-De Coninck R Wattiaux P Lobel 《The Journal of biological chemistry》1999,274(30):21104-21113
The intracellular transport of soluble lysosomal enzymes relies on the post-translational modification of N-linked oligosaccharides to generate mannose 6-phosphate (Man 6-P) residues. In most cell types the Man 6-P signal is rapidly removed after targeting of the precursor proteins from the Golgi to lysosomes via interactions with Man 6-phosphate receptors. However, in brain, the steady state proportion of lysosomal enzymes containing Man 6-P is considerably higher than in other tissues. As a first step toward understanding the mechanism and biological significance of this observation, we analyzed the subcellular localization of the rat brain Man 6-P glycoproteins by combining biochemical and morphological approaches. The brain Man 6-P glycoproteins are predominantly localized in neuronal lysosomes with no evidence for a steady state localization in nonlysosomal or prelysosomal compartments. This contrasts with the clear endosome-like localization of the low steady state proportion of mannose-6-phosphorylated lysosomal enzymes in liver. It therefore seems likely that the observed high percentage of phosphorylated species in brain is a consequence of the accumulation of lysosomal enzymes in a neuronal lysosome that does not fully dephosphorylate the Man 6-P moieties. 相似文献
125.
126.
Yang HC Lin CH Hsu CL Hung SI Wu JY Pan WH Chen YT Fann CS 《Journal of biomedical science》2006,13(4):489-498
Summary Genetic dissection of complex diseases is both important and challenging. The human major histocompatibility complex is involved in many human diseases and genetic mechanisms. This highly polymorphic chromosome region has been extensively studied in Caucasians but not as well in Asians. Thus, we compared genotypic distributions, linkage disequilibria and haplotype blocks between Caucasian and Taiwan’s Han Chinese populations. Moreover, we investigated the population admixture and phylogenetic system in Han Chinese residing in Taiwan. The results show that Taiwan’s Han Chinese differ drastically in genotypic information compared with Caucasians but are relatively homogeneous among the three major ethnic subgroups, Minnan, Hakka and Mainlanders. Differences in allele frequency (AF) between Taiwanese and Caucasians in some disease-associated loci may reveal clues to differences in disease prevalence. The results of ethnic heterogeneity imply that public databases should be used with caution in cases where the study population(s) differs from the population characterized in the database. The high homogeneity we observed among the Taiwanese subpopulations mitigates the possibility of spurious association caused by ignoring population stratification in Taiwanese disease gene association studies. These results are useful for understanding our genetic background and designing future disease gene mapping studies.Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users. 相似文献
127.
A novel in vitro retinal differentiation model by co-culturing adult human bone marrow stem cells with retinal pigmented epithelium cells 总被引:4,自引:0,他引:4
Chiou SH Kao CL Peng CH Chen SJ Tarng YW Ku HH Chen YC Shyr YM Liu RS Hsu CJ Yang DM Hsu WM Kuo CD Lee CH 《Biochemical and biophysical research communications》2005,326(3):578-585
Human retinal pigment epithelium (HRPE) cells are important in maintaining the normal physiology within the neurosensory retina and photoreceptors. Recently, transplantation of HRPE has become a possible therapeutic approach for retinal degeneration. By negative immunoselection (CD45 and glycophorin A), in this study, we have isolated and cultivated adult human bone marrow stem cells (BMSCs) with multilineage differentiation potential. After a 2- to 4-week culture under chondrogenic, osteogenic, adipogenic, and hepatogenic induction medium, these BMSCs were found to differentiate into cartilage, bone, adipocyte, and hepatocyte-like cells, respectively. We also showed that these BMSCs could differentiate into neural precursor cells (nestin-positive) and mature neurons (MAP-2 and Tuj1-positive) following treatment of neural selection and induction medium for 1 month. Furthermore, the plasticity of BMSCs was confirmed by initiating their differentiation into retinal cells and photoreceptor lineages by co-culturing with HRPE cells. The latter system provides an ex vivo expansion model of culturing photoreceptors for the treatment of retinal degeneration diseases. 相似文献
128.
Hsu CH Chang MD Tai KY Yang YT Wang PS Chen CJ Wang YH Lee SC Wu CW Juan LJ 《The EMBO journal》2004,23(11):2269-2280
Targeting of cellular histone acetyltransferases (HATs) by viral proteins is important in the development of virus-associated diseases. The immediate-early 2 protein (IE2) of human cytomegalovirus (HCMV) binds to the tumor suppressor, p53, and inactivates its functions by unknown mechanisms. Here, we show that IE2 binds to the HAT domain of the p53 coactivators, p300 and CREB-binding protein (CBP), and blocks their acetyltransferase activity on both histones and p53. The minimal HAT inactivation region on IE2 involves the N-terminal 98 amino acids. The in vivo DNA binding of p53 and local histone acetylation on p53-dependent promoters are all reduced by IE2, but not by mutant IE2 proteins that lack the HAT inhibition region. Furthermore, the p53 acetylation site mutant, K320/373/382R, retains both DNA binding and promoter transactivation activity in vivo and these effects are repressed by IE2 as well. Together with the finding that only wild-type IE2 exerts an antiapoptotic effect, our results suggest that HCMV IE2 downregulates p53-dependent gene activation by inhibiting p300/CBP-mediated local histone acetylation and that IE2 may have oncogenic activity. 相似文献
129.
Tsai‐Ching Hsu Chun‐Ching Chiu Yi‐Wen Wang Bor‐Show Tzang 《Journal of cellular and molecular medicine》2013,17(10):1308-1315
Attenuated antioxidant activities, irregular cytokines expressions and reduced regulatory T cells, are strongly associated with the pathogenesis of systemic lupus erythematosus (SLE). Despite the well‐established beneficial effects of cystamine on lupus‐prone mice, the extent to which cystamine contributes to antioxidant activity and the reduction of regulatory T cells has seldom been investigated. Therefore, this study elucidates how cystamine affects anti‐oxidant activities in NZB/W F1 mice by performing assays of Glutathione (GSH), 1,1‐diphenyl‐2‐ picryl‐hydrazyl (DPPH) and malondialdehyde thiobarbituric acid (MDA). In addition, investigations of the effects of cystamine on CD4+/CD25+ regulatory T cells and interleukin‐6 (IL6)/STAT‐3 signalling were performed with flow cytometry and immunoblots. Experimental results reveal more significantly reduced MDA and increased GSH and DPPH in NZB/W F1 mice receiving cystamine than in those mice receiving PBS. Meanwhile, CD4+/CD25+ regulatory T cells more significantly increase in NZB/W F1 mice receiving cystamine than in those mice receiving PBS, accompanied by significantly reduced IL‐6/phosphorylated STAT‐3 expression. The above findings suggest the beneficial effects of cystamine in terms of increasing antioxidant activities and CD4+/CD25+ regulatory T cells in lupus‐prone mice by suppressing IL‐6/STAT3 signalling. 相似文献
130.