全文获取类型
收费全文 | 582篇 |
免费 | 69篇 |
国内免费 | 2篇 |
出版年
2021年 | 5篇 |
2016年 | 4篇 |
2015年 | 15篇 |
2014年 | 9篇 |
2013年 | 19篇 |
2012年 | 18篇 |
2011年 | 15篇 |
2010年 | 14篇 |
2009年 | 10篇 |
2008年 | 14篇 |
2007年 | 18篇 |
2006年 | 18篇 |
2005年 | 10篇 |
2004年 | 21篇 |
2003年 | 18篇 |
2002年 | 28篇 |
2001年 | 20篇 |
2000年 | 16篇 |
1999年 | 23篇 |
1998年 | 15篇 |
1997年 | 19篇 |
1996年 | 9篇 |
1995年 | 10篇 |
1994年 | 6篇 |
1993年 | 11篇 |
1992年 | 28篇 |
1991年 | 26篇 |
1990年 | 24篇 |
1989年 | 20篇 |
1988年 | 9篇 |
1987年 | 10篇 |
1986年 | 10篇 |
1985年 | 14篇 |
1984年 | 19篇 |
1983年 | 7篇 |
1982年 | 10篇 |
1981年 | 8篇 |
1980年 | 4篇 |
1979年 | 13篇 |
1978年 | 9篇 |
1977年 | 11篇 |
1976年 | 12篇 |
1975年 | 5篇 |
1974年 | 10篇 |
1973年 | 9篇 |
1972年 | 11篇 |
1970年 | 2篇 |
1969年 | 3篇 |
1968年 | 2篇 |
1967年 | 2篇 |
排序方式: 共有653条查询结果,搜索用时 171 毫秒
41.
42.
43.
44.
Yoshimasa Ishizaki Chigusa Hayashi Kunio Inoue Masayuki Igarashi Yoshiaki Takahashi Venugopal Pujari Dean C. Crick Patrick J. Brennan Akio Nomoto 《The Journal of biological chemistry》2013,288(42):30309-30319
Because tuberculosis is one of the most prevalent and serious infections, countermeasures against it are urgently required. We isolated the antitubercular agents caprazamycins from the culture of an actinomycete strain and created CPZEN-45 as the most promising derivative of the caprazamycins. Herein, we describe the mode of action of CPZEN-45 first against Bacillus subtilis. Unlike the caprazamycins, CPZEN-45 strongly inhibited incorporation of radiolabeled glycerol into growing cultures and showed antibacterial activity against caprazamycin-resistant strains, including a strain overexpressing translocase-I (MraY, involved in the biosynthesis of peptidoglycan), the target of the caprazamycins. By contrast, CPZEN-45 was not effective against a strain overexpressing undecaprenyl-phosphate–GlcNAc-1-phosphate transferase (TagO, involved in the biosynthesis of teichoic acid), and a mutation was found in the tagO gene of the spontaneous CPZEN-45-resistant strain. This suggested that the primary target of CPZEN-45 in B. subtilis is TagO, which is a different target from that of the parent caprazamycins. This suggestion was confirmed by evaluation of the activities of these enzymes. Finally, we showed that CPZEN-45 was effective against WecA (Rv1302, also called Rfe) of Mycobacterium tuberculosis, the ortholog of TagO and involved in the biosynthesis of the mycolylarabinogalactan of the cell wall of M. tuberculosis. The outlook for WecA as a promising target for the development of antituberculous drugs as a countermeasure of drug resistant tuberculosis is discussed. 相似文献
45.
Caspase-independent cell death and mitochondrial disruptions observed in the Apaf1-deficient cells 总被引:3,自引:0,他引:3
Miyazaki K Yoshida H Sasaki M Hara H Kimura G Mak TW Nomoto K 《Journal of biochemistry》2001,129(6):963-969
Apaf1 is a critical molecule in the mitochondria-dependent apoptotic pathway. Here we show that Apaf1-deficient embryonic fibroblasts died at a later phase of apoptotic induction, although these cells were resistant to various apoptotic stimulants at an early phase. Neither caspase 3 activation nor nuclear condensation was observed during this cell death of Apaf1-deficient cells. Electron microscopic examination revealed that death in response to apoptotic stimulation resembled necrosis in that nuclei were round and swollen with low electron density. Necrosis-like cell death was also observed in wild-type cells treated with z-VAD-fmk. Mitochondria were not only morphologically abnormal but functionally affected, since mitochondrial transmembrane potential (DeltaPsim) was lost even in cells with intact plasma membrane integrity. These mitochondrial alterations were also observed in the wild-type cells dying of apoptosis. Combined, these data suggest that cells without caspase activation, such as Apaf1-deficient cells or cells treated with caspase inhibitors, die of necrosis-like cell death with mitochondrial damage in response to "apoptotic stimulation." 相似文献
46.
Morikane K Tempero RM Sivinski CL Nomoto M Van Lith ML Muto T Hollingsworth MA 《Cancer immunology, immunotherapy : CII》1999,47(5):287-296
We established a model of orthotopic injection of a syngeneic pancreatic tumor cell line in C57BL/6 mice and evaluated the
effects of organ site on induction of immunity to a tumor-specific antigen, MUC1. Mice were challenged with a syngeneic pancreatic
adenocarcinoma cell line that expressed MUC1 (Panc02-MUC1) by orthotopic injection into the pancreas, or by subcutaneous injection.
Tumor cells injected into the pancreas grew much faster than those injected subcutaneously. Mice challenged subcutaneously
with Panc02-MUC1 rejected tumors or developed slowly growing tumors that were negative for MUC1 expression. In contrast, mice
challenged orthotopically into the pancreas developed progressive tumors that were positive for MUC1 expression. Sera from
mice that rejected Panc02-MUC1 (tumor-immune mice) showed no detectable IgG1 and IgM titers against the MUC1 tandem-repeat
peptide, whereas mice with progressive tumor growth had significant titers of IgG1 and IgM specific for MUC1. This suggests
that the humoral immune response was ineffective in mediating tumor rejection. The results show that the growth properties
and immunological rejection of pancreatic tumors is affected by the organ site at which the tumor grows.
Received: 25 April 1998 / Accepted: 7 October 1998 相似文献
47.
Slugs can retain odor-taste associative memory for several weeks, and this requires protein synthesis. We examined the dose-dependency of the onset time of amnesia caused by the protein synthesis inhibitor anisomycin, and showed that with reduced dose, the onset is shifted from 2 days to 3 days after conditioning; we could not shift the onset delay later than 3 days. Our results suggest that the mechanism underling memory retention is different in the period up to 3 days, versus the period later than 3 days. Our results also suggest that sustained inhibition of protein synthesis in the period from zero to 3 hr after conditioning is necessary to cause amnesia. 相似文献
48.
Tissue-specific replicating capacity of a chimeric poliovirus that carries the internal ribosome entry site of hepatitis C virus in a new mouse model transgenic for the human poliovirus receptor
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Yanagiya A Ohka S Hashida N Okamura M Taya C Kamoshita N Iwasaki K Sasaki Y Yonekawa H Nomoto A 《Journal of virology》2003,77(19):10479-10487
Nucleotides (nt) 108 to 742 of an infectious cDNA clone of poliovirus (PV) Mahoney strain, including the corresponding region of the internal ribosome entry site (IRES), was replaced by nt 28 to 710 of hepatitis C virus (HCV) cDNA corresponding to the whole HCV IRES. A chimeric PV (2A-369) was generated by transfecting mammalian cells with an RNA transcribed in vitro from the cDNA. To examine replicating capacity of virus 2A-369 in the brain and liver of a mouse model for poliomyelitis, a new mouse model (MPVRTg25-61) that is transgenic for human PV receptor (hPVR; CD155) was generated in order to obtain a higher expression level of hPVR in the liver than those of hPVRTg mouse lines generated by us so far. The transgene used was constructed by combining a putative regulatory region of the mouse PVR homolog and the whole structural region of the hPVR gene. Virus 2A-369 replicated well in the liver of MPVRTg25-61 but not in the brain, whereas control Mahoney virus replicated well both in the liver and in the brain. The data suggest that the HCV IRES works more efficiently in the liver than in the brain and that PV IRES works well both in the liver and in the brain. The results support the notion that tissue-specific activity of IRES may be reflected in tissue tropism of a virus whose specific translation initiation is driven by IRES, that is, an IRES-dependent virus tropism. 相似文献
49.
Siegel DH Ashton GH Penagos HG Lee JV Feiler HS Wilhelmsen KC South AP Smith FJ Prescott AR Wessagowit V Oyama N Akiyama M Al Aboud D Al Aboud K Al Githami A Al Hawsawi K Al Ismaily A Al-Suwaid R Atherton DJ Caputo R Fine JD Frieden IJ Fuchs E Haber RM Harada T Kitajima Y Mallory SB Ogawa H Sahin S Shimizu H Suga Y Tadini G Tsuchiya K Wiebe CB Wojnarowska F Zaghloul AB Hamada T Mallipeddi R Eady RA McLean WH McGrath JA Epstein EH 《American journal of human genetics》2003,73(1):174-187
Kindler syndrome is an autosomal recessive disorder characterized by neonatal blistering, sun sensitivity, atrophy, abnormal pigmentation, and fragility of the skin. Linkage and homozygosity analysis in an isolated Panamanian cohort and in additional inbred families mapped the gene to 20p12.3. Loss-of-function mutations were identified in the FLJ20116 gene (renamed “KIND1” [encoding kindlin-1]). Kindlin-1 is a human homolog of the Caenorhabditis elegans protein UNC-112, a membrane-associated structural/signaling protein that has been implicated in linking the actin cytoskeleton to the extracellular matrix (ECM). Thus, Kindler syndrome is, to our knowledge, the first skin fragility disorder caused by a defect in actin-ECM linkage, rather than keratin-ECM linkage. 相似文献
50.
Taketani Y Nomoto M Yamamoto H Isshiki M Morita K Arai H Miyamoto K Kato S Takeda E 《Biochemical and biophysical research communications》2003,305(2):287-291
The mechanisms by which Pi depletion rapidly regulates gene expression and cellular function have not been clarified. Here, we found a rapid increase in intracellular ionized calcium [Ca(2+)](i) by phosphate depletion in LLC-PK(1) cells using confocal microscopy with the green-fluorescence protein based calcium indicator "yellow cameleon 2.1." The increase of [Ca(2+)](i) was observed in the presence or absence of extracellular Ca(2+). At the same time, an approximately twofold increase in intracellular inositol 1,4,5-triphosphate (IP(3)) occurred in response to the acute Pi depletion in the medium. Furthermore, 2-aminoethoxydiphenyl borate completely blocked the [Ca(2+)](i) increase induced by Pi depletion. These results suggest that Pi depletion causes IP(3)-mediated release of Ca(2+) from intracellular Ca(2+) pools and rapidly increases [Ca(2+)](i) in LLC-PK(1) cells. 相似文献