全文获取类型
收费全文 | 1088篇 |
免费 | 93篇 |
出版年
2021年 | 11篇 |
2020年 | 8篇 |
2019年 | 8篇 |
2018年 | 17篇 |
2017年 | 11篇 |
2016年 | 21篇 |
2015年 | 25篇 |
2014年 | 34篇 |
2013年 | 59篇 |
2012年 | 54篇 |
2011年 | 54篇 |
2010年 | 40篇 |
2009年 | 39篇 |
2008年 | 61篇 |
2007年 | 54篇 |
2006年 | 48篇 |
2005年 | 39篇 |
2004年 | 41篇 |
2003年 | 35篇 |
2002年 | 44篇 |
2001年 | 33篇 |
2000年 | 51篇 |
1999年 | 45篇 |
1998年 | 26篇 |
1997年 | 21篇 |
1996年 | 15篇 |
1995年 | 9篇 |
1994年 | 6篇 |
1993年 | 5篇 |
1992年 | 22篇 |
1991年 | 17篇 |
1990年 | 30篇 |
1989年 | 21篇 |
1988年 | 17篇 |
1987年 | 23篇 |
1986年 | 14篇 |
1985年 | 5篇 |
1984年 | 15篇 |
1983年 | 8篇 |
1982年 | 10篇 |
1981年 | 4篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1978年 | 7篇 |
1975年 | 11篇 |
1974年 | 5篇 |
1973年 | 5篇 |
1971年 | 9篇 |
1969年 | 8篇 |
1967年 | 6篇 |
排序方式: 共有1181条查询结果,搜索用时 15 毫秒
71.
72.
Sakurai N Wu JH Sashida Y Mimaki Y Nikaido T Koike K Itokawa H Lee KH 《Bioorganic & medicinal chemistry letters》2004,14(5):1329-1332
Actein (1), a tetracyclic triterpenoid from the rhizome of Cimicifuga racemosa (black cohosh), and 82 related triterpenoid and steroidal saponins isolated from higher plants were evaluated for anti-HIV activity as a continuing study to discover potential anti-AIDS agents from natural products. Actein showed potent activity and another twelve saponins showed moderate activity. The active compounds included two steroidal, seven tetracyclic triterpenoid, and four pentacyclic triterpenoid compounds. 相似文献
73.
Molecular microbial ecology of the gastrointestinal tract: from phylogeny to function 总被引:4,自引:0,他引:4
During the past decade it became evident that anaerobic cultivation-based approaches provides an incomplete picture of the microbial diversity in the GI tract, since at present only a minority of microbes can be obtained in culture. The application of molecular, mainly 16S ribosomal RNA (rRNA)-based approaches enables researchers to bypass the cultivation step and has proven its usefulness in studying the microbial composition in a variety of ecosystems, including the gastrointestinal (GI) tract. This critical review summarizes the impact of these culture-independent approaches on our knowledge of the ecology of the GI tract and provides directions for future studies which should emphasize function of specific strains, species and groups of microbes. 相似文献
74.
Fan J Wang X Wu L Matsumoto SI Liang J Koike T Ichikawa T Sun H Shikama H Sasaguri Y Watanabe T 《Transgenic research》2004,13(3):261-269
Increased matrix metalloproteinase-12 (MMP-12) has been implicated in atherosclerosis and many other inflammatory processes.
To define MMP-12 functions in vivo, we generated transgenic rabbits that expressed human (h) MMP-12 gene under the control of a macrophage-specific promoter,
the human scavenger receptor promoter. Two transgenic founder rabbits were found to have hMMP-12 transgene integration by
Southern blot analysis. hMMP-12 mRNA was expressed in peritoneal and alveolar macrophages, and in tissues enriched in macrophages
in transgenic rabbits. High levels of hMMP-12 protein were detected in the conditioned media of cultured peritoneal and alveolar
macrophages from transgenic rabbits. Zymography showed that hMMP-12 secreted from macrophages possessed enzymatic activity
toward β-casein. To evaluate the expression of hMMP-12 in inflammatory sites, we used carrageenan-induced granulomas as an
in vivo model for tissue macrophages and foam cells. Granuloma size in transgenic rabbits was significantly increased compared to
that in control rabbits, and histological examination revealed that granulomas of transgenic rabbits were enriched in macrophages
associated with increased hMMP-12 expression. We believe that this transgenic rabbit model with increased expression of hMMP-12
may become a useful model for further mechanistic studies of MMP-12 in inflammatory diseases and cancer invasion; it is also
an ideal model for testing the in vivo action of MMP-12 inhibitors. 相似文献
75.
Proteasome activator PA28gamma-dependent nuclear retention and degradation of hepatitis C virus core protein
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)
Moriishi K Okabayashi T Nakai K Moriya K Koike K Murata S Chiba T Tanaka K Suzuki R Suzuki T Miyamura T Matsuura Y 《Journal of virology》2003,77(19):10237-10249
Hepatitis C virus (HCV) core protein plays an important role in the formation of the viral nucleocapsid and a regulatory protein involved in hepatocarcinogenesis. In this study, we have identified proteasome activator PA28gamma (11S regulator gamma) as an HCV core binding protein by using yeast two-hybrid system. This interaction was demonstrated not only in cell culture but also in the livers of HCV core transgenic mice. These findings are extended to human HCV infection by the observation of this interaction in liver specimens from a patient with chronic HCV infection. Neither the interaction of HCV core protein with other PA28 subtypes nor that of PA28gamma with other Flavivirus core proteins was detected. Deletion of the PA28gamma-binding region from the HCV core protein or knockout of the PA28gamma gene led to the export of the HCV core protein from the nucleus to the cytoplasm. Overexpression of PA28gamma enhanced the proteolysis of the HCV core protein. Thus, the nuclear retention and stability of the HCV core protein is regulated via a PA28gamma-dependent pathway through which HCV pathogenesis may be exerted. 相似文献
76.
ARF tumor suppressor induces mitochondria-dependent apoptosis by modulation of mitochondrial Bcl-2 family proteins 总被引:5,自引:0,他引:5
A tumor suppressor gene product, ARF, sensitizes cells to apoptosis in the presence of appropriate collateral signals. In this study, we analyzed the mechanism of ARF-dependent apoptosis and demonstrated that ARF induces mitochondria-dependent apoptosis in p53 wild-type, ARF/p16-null cells. We also found that ARF evokes cytochrome c release from mitochondria, decreases mitochondrial membrane potential, and activates pro-caspase-9 to induce apoptosis. Our findings suggest that this apoptotic cellular modulation is brought about by up-regulation of the proapoptotic Bcl-2 family proteins Bax and Bim and down-regulation of antiapoptotic Bcl-2 in mitochondrial fractions. Additionally, ARF seems to down-regulate Bcl-2 in a p53-dependent manner while up-regulating Bax/Bim via a p53-independent pathway. 相似文献
77.
Recovery processes of photosynthetic systems during rewetting were studied in detail in a terrestrial, highly drought-tolerant cyanobacterium, Nostoc commune. With absorption of water, the weight of N. commune colony increased in three phases with half-increase times of about 1 min, 2 h and 9 h. Fluorescence intensities of phycobiliproteins and photosystem (PS) I complexes were recovered almost completely within 1 min, suggesting that their functional forms were restored very quickly. Energy transfer from allophycocyanin to the core-membrane linker peptide (L(CM)) was recovered within 1 min, but not that from L(CM) to PSII. PSI activity and cyclic electron flow around PSI recovered within 2 min, while the PSII activity recovered in two phases after a time lag of about 5 min, with half times of about 20 min and 2 h. Photosynthetic CO(2) fixation was restored almost in parallel with the first recovery phase of the PSII reaction center activity. Although the amount of absorbed water became more than 20 times the initial dry weight of the N. commune colony in the presence of sufficient water, about twice the initial dry weight was enough for recovery and maintenance of the PSII activity. 相似文献
78.
Kashino Y Koike H Yoshio M Egashira H Ikeuchi M Pakrasi HB Satoh K 《Plant & cell physiology》2002,43(11):1366-1373
Using a recently introduced electrophoresis system [Kashino et al. (2001) Electrophoresis 22: 1004], components of low-molecular-mass polypeptides were analyzed in detail in photosystem II (PSII) complexes isolated from a thermophilic cyanobacterium, Thermosynechococcus vulcanus (formerly, Synechococcus vulcanus). PsbE, the large subunit polypeptide of cytochrome b(559), showed an apparent molecular mass much lower than the expected one. The unusually large mobility could be attributed to the large intrinsic net electronic charge. All other Coomassie-stained polypeptides were identified by N-terminal sequencing. In addition to the well-known cyanobacterial PSII polypeptides, such as PsbE, F, H, I, L, M, U, V and X, the presence of PsbY, PsbZ and Psb27 was also confirmed in the isolated PSII complexes. Furthermore, the whole amino acid sequence was determined for the polypeptide which was known as PsbN. The whole amino acid sequence revealed that this polypeptide was identical to PsbTc which has been found in higher plants and green algae. These results strongly suggest that PsbN is not a member of the PSII complex. It is also shown that cyanobacteria have cytochrome b(559) in the high potential form as in higher plants. 相似文献
79.
The isolation of mutant cells with phenotypes caused by random mutagenesis has been hampered in mammalian cells because there are two alleles per gene and the disruption of both alleles is extremely rare. We describe a method for the efficient biallelic mutagenesis in embryonic stem cells. loxP sites were introduced near the centromeric regions of a pair of chromosome 1s. A mutant neo gene was inserted at the distal part of one of the loxP sites so that biallelic mutants would be selected by high-dose G418. Expression of Cre induced the recombination between homologous chromosomes and led to an elevation in the number of biallelic mutants. This system will facilitate phenotype-driven gene function study in the mammalian system. 相似文献
80.
We examined whether interleukin (IL)-6 exerts the stimulatory effects on the secretion of histamine from human mast cells triggered by crosslinking of the high affinity IgE receptor (FcepsilonRI) with IgE and anti-IgE. As target cells, we used peripheral blood-derived cultured mast cells grown with SCF, because they were superior in FcepsilonRIalpha expression to cord blood-derived mast cells. Incubation with SCF+IL-6 for 1 week increased the IgE-dependent release as well as intracellular content of histamine in the cultured mast cells, as compared with the values obtained by incubation with SCF alone. The magnitude of these increases was higher than that for priming with SCF+IL-4. A striking difference was also found in the expression of FcepsilonRIalpha between the two-factor combinations. The addition of IL-6 during FcepsilonRI crosslinking with IgE/anti-IgE in the presence of SCF did not influence histamine secretion. When SCF, IL-6 and IL-4 were used together, a further increase was observed in the anti-IgE-dependent liberation of histamine from the cultured mast cells, compared with the two-factor combinations. These results suggest that IL-6 functions as a secretagogue for the inflammatory mediator of human mast cells in the presence of SCF. 相似文献