全文获取类型
收费全文 | 298篇 |
免费 | 19篇 |
专业分类
317篇 |
出版年
2024年 | 1篇 |
2023年 | 5篇 |
2022年 | 5篇 |
2021年 | 8篇 |
2020年 | 6篇 |
2019年 | 8篇 |
2018年 | 4篇 |
2017年 | 7篇 |
2016年 | 18篇 |
2015年 | 9篇 |
2014年 | 10篇 |
2013年 | 20篇 |
2012年 | 21篇 |
2011年 | 25篇 |
2010年 | 11篇 |
2009年 | 12篇 |
2008年 | 9篇 |
2007年 | 12篇 |
2006年 | 16篇 |
2005年 | 12篇 |
2004年 | 15篇 |
2003年 | 14篇 |
2002年 | 7篇 |
2001年 | 8篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 1篇 |
1997年 | 5篇 |
1996年 | 2篇 |
1993年 | 4篇 |
1992年 | 1篇 |
1989年 | 4篇 |
1986年 | 1篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1973年 | 2篇 |
1972年 | 3篇 |
1970年 | 2篇 |
1968年 | 5篇 |
1967年 | 1篇 |
排序方式: 共有317条查询结果,搜索用时 0 毫秒
101.
Eda Acikgoz Ummu Guven Fahriye Duzagac Ruchan Uslu Mikail Kara Burak Cem Soner Gulperi Oktem 《PloS one》2015,10(10)
Trabectedin (Yondelis, ET-743) is a marine-derived tetrahydroisoquinoline alkaloid. It is originally derived from the Caribbean marine tunicate Ecteinascidia turbinata and currently produced synthetically. Trabectedin is active against a variety of tumor cell lines growing in culture. The present study focused on the effect of trabectedin in cell proliferation, cell cycle progression, apoptosis and spheroid formation in prostate cancer stem cells (CSCs). Cluster of differentiation (CD) 133+high/CD44+high prostate CSCs were isolated from the DU145 and PC-3 human prostate cancer cell line through flow cytometry. We studied the growth-inhibitory effects of trabectedin and its molecular mechanisms on human prostate CSCs and non-CSCs. DU-145 and PC-3 CSCs were treated with 0.1, 1, 10 and 100 nM trabectedin for 24, 48 and 72 h and the growth inhibition rates were examined using the sphere-forming assay. Annexin-V assay and immunofluorescence analyses were performed for the detection of the cell death. Concentration-dependent effects of trabectedin on the cell cycle were also evaluated. The cells were exposed to the different doses of trabectedin for 24, 48 and 72 h to evaluate the effect of trabectedin on the number and diameter of spheroids. According to the results, trabectedin induced cytotoxicity and apoptosis at the IC50 dose, resulting in a significant increase expression of caspase-3, caspase-8, caspase-9, p53 and decrease expression of bcl-2 in dose-dependent manner. Cell cycle analyses revealed that trabectedin induces dose-dependent G2/M-phase cell cycle arrest, particularly at high-dose treatments. Three-dimensional culture studies showed that trabectedin reduced the number and diameter of spheroids of DU145 and PC3 CSCs. Furthermore, we have found that trabectedin disrupted cell-cell interactions via E-cadherin in prostasphere of DU-145 and PC-3 CSCs. Our results showed that trabectedin inhibits cellular proliferation and accelerates apoptotic events in prostate CSCs; and may be a potential effective therapeutic agent against prostate cancer. 相似文献
102.
Yukari Okamoto Koichi Shiosaki Yasuyuki Eda Sachio Tokiyoshi Yumi Yamaguchi Takashi Gojobori Takashi Hachimori Shudo Yamazaki Mitsuo Honda 《Microbiology and immunology》1997,41(2):131-138
The sequences of the V3 loop and surrounding regions of human immunodeficiency virus type-1 from a father-to-mother-to-infant trimmer were studied and the horizontal and vertical transmissions compared. The father's virus was variable for reactivity with neutralizing antibody and sequences of the V3 loop central core sequence. In contrast, the mother's viral sequences were much less diverse and reacted with a virus neutralizing antibody. The infant's viral sequences were also less diverse than those of the father, and N-glycosylation sites were conserved. By phylogenetic analysis, the major clone, of which V3-peptide reacted with the neutralizing antibody, was found to be transmitted from the mother to her infant; however, the mutated minor clones did not bind to the antibody. These findings suggest that both horizontal and vertical virus transmission were selective, and that the clonally transmitted virus in infants mutates more rapidly than viruses in the mother, to whom the virus was horizontally transmitted. 相似文献
103.
Baykal-Caglar E Hassan-Zadeh E Saremi B Huang J 《Biochimica et biophysica acta》2012,1818(11):2598-2604
Giant unilamellar vesicles (GUVs) containing cholesterol often have a wide distribution in lipid composition. In this study, GUVs of 1,2-dioleoyl-sn-glycero-3-phosphocholine(DOPC)/1,2-distearoyl-sn-glycero-3-phosphocholine(DSPC)/cholesterol and 1,2-diphytanoyl-sn-glycero-3-phosphocholine(diPhyPC)/1,2-dipalmitoyl-sn-glycero-3-phosphocholine(DPPC)/cholesterol were prepared from dry lipid films using the standard electroformation method as well as a modified method from damp lipid films, which are made from compositional uniform liposomes prepared using the Rapid Solvent Exchange (RSE) method. We quantified the lipid compositional distributions of GUV by measuring the miscibility transition temperature of GUVs using fluorescence microscopy, since a narrower distribution in the transition temperature should correspond to a more uniform distribution in GUV lipid composition. Cholesterol molecules can demix from other lipids in dry state and form cholesterol crystals. Using optical microscopy, micron-sized crystals were observed in some dry lipid films. Thus, a major cause of GUV lipid compositional heterogeneity is the demixing of lipids in the dry film state. By avoiding the dry film state, GUVs prepared from damp lipid films have a better uniformity in lipid composition, and the standard deviations of miscibility transition temperature are about 2.5 times smaller than that of GUVs prepared from dry lipid films. Comparing the two ternary systems, diPhyPC/DPPC/cholesterol GUVs has a larger cholesterol compositional heterogeneity, which directly correlates with the low maximum solubility of cholesterol in diPhyPC lipid bilayers (40.2±0.5mol%) measured by light scattering. Our data indicate that cholesterol interacts far less favorably with diPhyPC than it does with other PCs. The damp lipid film method also has a potential of preparing GUVs from cell membranes containing native proteins without going through a dry state. 相似文献
104.
Gabriela Vanina Villanova Manuel Vera Florencia Brancolini Juan Díaz Paulino Martinez Silvia Eda Arranz 《Hydrobiologia》2018,824(1):243-254
Since 2013, the pelagic zone of Upper Lake Constance (ULC) has been subject to a massive invasion of the non-native three-spined stickleback (Gasterosteus aculeatus Linnaeus, 1758). Data from monthly monitoring of pelagic whitefish (Coregonus wartmanni Bloch, 1784) were used to compare weight-at-age and abundance of pelagic whitefish for years before (1997–2012) and after the invasion (2013–2015). Growth and abundance of pelagic whitefish is shown to be heavily influenced by stickleback presence. Mean autumn weight-at-age of whitefish decreased by 33.3% after the invasion took place and a significant decline in autumn CPUE in otherwise unfished cohorts of the population was also recorded. The results imply direct effects of stickleback presence on pelagic whitefish, including interspecific competition for food leading to reduced growth and survival, and predation of eggs and larvae, hampering recruitment. These observations coincide with a sharp decline in whitefish yield. In conclusion, this study shows that the invasion of stickleback has substantially altered the pelagic fish community of ULC, with severe consequences for commercial fisheries. 相似文献
105.
Infected erythrocytes containing the more mature stages of the human malaria Plasmodium falciparum may adhere to endothelial cells and uninfected red cells. These phenomena, called sequestration and rosetting, respectively, are involved in both host pathogenesis and parasite survival. This review provides a critical summary of recent advances in the characterization of the molecules of the infected red blood cell involved in adhesion, i.e. parasite-encoded molecules (PfEMP1, MESA, rifins, stevor, clag 9, histidine-rich protein), a modified host membrane protein (band 3) and exofacial exposure of phosphatidylserine, as well as receptors on the endothelium, i.e. thrombospondin, CD36, ICAM-1 (intercellular adhesion molecule), and chondroitin sulfate. 相似文献
106.
Protein-based complex medium design for recombinant serine alkaline protease production 总被引:2,自引:0,他引:2
Pnar alk Eda elik lkin E. Telli Ceren Oktar Elif
zdemir 《Enzyme and microbial technology》2003,33(7):975-986
This work reports on the design of a complex medium based on simple and complex carbon sources, i.e. glucose, sucrose, molasses, and defatted-soybean, and simple and complex nitrogen sources, i.e. (NH4)2HPO4, casein, and defatted-soybean, for serine alkaline protease (SAP) production by recombinant Bacillus subtilis carrying pHV1431::subC gene. SAP activity was obtained as 3050 U cm−3 with the initial defatted-soybean concentration Csoybeano=20 kg m−3 and initial glucose concentration CGo=8 kg m−3; whereas, addition of the inorganic nitrogen source (NH4)2HPO4 decreased SAP production considerably. Further increase in SAP production (3850 U cm−3) was obtained when sucrose was replaced with glucose at Csucroseo=15 kg m−3 and Csoybeano=20 kg m−3. Nevertheless, when molasses was replaced with sucrose, the maximum activity was obtained with molasses having 10 kg m−3 initial sucrose concentration and Csoybeano=15 kg m−3as 2130 U cm−3; moreover, when casein was replaced with defatted-soybean SAP production decreased considerably (ca. 250 U cm−3). Thereafter, the effects of inorganic ionic compounds were investigated; and except phosphate, inorganic compounds supplied from defatted-soybean were found to be sufficient for the bioprocess. The highest SAP activity was obtained as 5350 U cm−3 in the medium that contained (kg m−3): Csoybeano=20, Csucroseo=15, CNa2HPO4o=0.021, and CNaH2PO4o=2.82, that was 6.5-fold higher than that of the SAP produced in the defined medium. By using the designed complex medium, oxygen transfer characteristics of the bioprocess were investigated; and, Damköhler number that is the oxygen transfer limitation increases with the cultivation time until t=14 h; and, at t>20 h both mass transfer and biochemical reaction resistances were effective. Overall oxygen transfer coefficient varied between 0.010 and 0.044 s−1; volumetric oxygen uptake rate varied between 0.001 and 0.006 mol m−3 s−1; and specific oxygen uptake rate varied between 0.0001 and 0.0022 mol kg−1 DW s−1 throughout the bioprocess. 相似文献
107.
Shigeru Eda Kunio Katō Atushi Ishizu Junzo Nakano 《Bioscience, biotechnology, and biochemistry》2013,77(7):1783-1790
An acidic polysaccharide (APS-H) purified from the hemicellulosic fraction of the midrib of Nicotiana tabacum was composed of d-galacturonic acid, l-rhamnose, l-arabinose and d-galactose in a molar ratio of 31.8: 15.4: 9.9: 42.9. Its molecular weight was estimated to be 90,000 by gel filtration chromatography. APS-H had a pectin-like structure in which the rhamnogalacturonan backbone was composed of (1 → 2)-linked l-rhamnopyranosyl and (1 → 4)-linked d-galacturonosyl residues in a ratio of approximately 1: 2.1. It also contained (1 → 4)-linked d-galactan and (1 → 5)-linked l-arabinofuranosyl moieties as the side chains. Branch points occurred mainly at C-4 of (1 → 2)-linked l-rhamnosyl residues in the backbone and at C-6 of (1 → 4)-linked d-galactosyl residues in the side chains. 相似文献
108.
109.
Reproduction in the Mediterranean endemic gorgonian Spinimuricea klavereni (Anthozoa,Octocorallia, Plexauridae) 下载免费PDF全文
Spinimuricea klavereni is a Mediterranean endemic gorgonian that is rarely encountered, probably because it typically occurs at depths below 50 m. It is exceptionally common in the northern Marmara Sea, with an unusually shallow upper depth limit of ~20 m. The reproductive biology of this species was studied during a one year period off Büyükada, in the northeastern Marmara Sea. Spinimuricea klavereni is a gonochoric broadcast spawner with an almost even sex ratio. Colonies were ~15 cm in height at first reproduction. Gametogenesis was continuous, characterized by high male and female fecundities year‐round. Oocytes and sperm sacs of all developmental stages were found throughout the year, with small‐sized oocytes and sperm sacs dominant throughout the year. The reproduction of S. klavereni did not seem to exhibit any marked seasonal pattern, unlike most other studied Mediterranean octocorals. Modest variation in gamete output was probably related to slight alterations in food availability and temperature. The non‐seasonal reproductive pattern we observed may be related to the low intra‐annual variation in temperature in the Marmara Sea, and the fact that the mesotrophic‐eutrophic level of productivity in the Marmara Sea can support the energetic requirements of continuous gametogenesis in this gorgonian. Whether these patterns are local adaptations or intrinsic characteristics for this Mediterranean endemic species remains to be studied. 相似文献
110.
Eto K Eda K Kanemoto S Abe S 《Biochemical and biophysical research communications》2006,350(2):263-271
Neuregulin1 (NRG1) is a growth factor that signals through the interaction of the epidermal growth factor (EGF)-like domain with ErbB receptors. An immunoglobulin (Ig)-like domain is contained together with EGF-like domain in the ectodomain of some isoforms generated by alternative splicing, but its role in NRG1 signaling remained unclear. In the present study, we identified a novel isoform of NRG1 containing an Ig-like domain conserved among species from adult Xenopus laevis, which is predominantly expressed in the testis and brain. We generated recombinant proteins for the whole ectodomain and EGF-like domain alone of the isoform to compare their effects on cell proliferation, and phosphorylation of and their association with ErbB receptor, demonstrating that the ectodomain had approximately 10(3)-fold higher abilities than the EGF-like domain. Therefore, the Ig-like domain is probably essential for efficient interaction of an EGF-like domain with ErbB receptors. 相似文献