全文获取类型
收费全文 | 864篇 |
免费 | 47篇 |
出版年
2022年 | 6篇 |
2021年 | 13篇 |
2020年 | 9篇 |
2019年 | 9篇 |
2018年 | 18篇 |
2017年 | 9篇 |
2016年 | 22篇 |
2015年 | 32篇 |
2014年 | 25篇 |
2013年 | 44篇 |
2012年 | 46篇 |
2011年 | 43篇 |
2010年 | 30篇 |
2009年 | 37篇 |
2008年 | 45篇 |
2007年 | 40篇 |
2006年 | 42篇 |
2005年 | 36篇 |
2004年 | 49篇 |
2003年 | 48篇 |
2002年 | 33篇 |
2001年 | 26篇 |
2000年 | 25篇 |
1999年 | 17篇 |
1998年 | 9篇 |
1996年 | 3篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1993年 | 4篇 |
1992年 | 18篇 |
1991年 | 16篇 |
1990年 | 12篇 |
1989年 | 14篇 |
1988年 | 10篇 |
1987年 | 9篇 |
1986年 | 9篇 |
1985年 | 7篇 |
1983年 | 9篇 |
1982年 | 5篇 |
1980年 | 6篇 |
1979年 | 5篇 |
1978年 | 6篇 |
1977年 | 8篇 |
1976年 | 7篇 |
1974年 | 3篇 |
1973年 | 5篇 |
1972年 | 6篇 |
1971年 | 3篇 |
1969年 | 5篇 |
1968年 | 4篇 |
排序方式: 共有911条查询结果,搜索用时 750 毫秒
91.
Ribosomal biogenesis is correlated with cell cycle, cell proliferation, cell growth and tumorigenesis. Some oncogenes and tumor suppressors are involved in regulating the formation of mature ribosome and affecting the ribosomal biogenesis. In previous studies, the mitochondrial ribosomal protein L41 was reported to be involved in cell proliferation regulating through p21(WAF1/CIP1) and p53 pathway. In this report, we have identified a mitochondrial ribosomal protein S36 (mMRPS36), which is localized in the mitochondria, and demonstrated that overexpression of mMRPS36 in cells retards the cell proliferation and delays cell cycle progression. In addition, the mMRPS36 overexpression induces p21(WAF1/CIP1) expression, and regulates the expression and phosphorylation of p53. Our result also indicate that overexpression of mMRPS36 affects the mitochondrial function. These results suggest that mMRPS36 plays an important role in mitochondrial ribosomal biogenesis, which may cause nucleolar stress, thereby leading to cell cycle delay. 相似文献
92.
Park CW Yang JH Ah CS Ahn CG Choi YH Chung KH Kim WJ Sung GY 《Biosensors & bioelectronics》2011,29(1):219-223
We propose a new type of photosensitive biosensor with a CMOS compatible Si photodiode integrated circuit, for the high-sensitive detection of small mycotoxin molecules requiring competitive assay approach. In this work, a photodiode is connected to the gate of a field effect transistor (FET) so that the open circuit voltage (V(OC)) of the illuminated photodiode is transferred into the drain/source current (I(DS)) of the FET. The sensing scheme employs competitive binding of toxin molecules (within the sample solution) and toxin-BSA conjugates (immobilized on the photodiode surface) with Au-nanoparticle-labeled antibodies, followed by silver enhancement to generate opaque structures on the photodiode surface. By utilizing the non-linear dependence of the V(OC) on the light intensity, we can maintain a sufficiently high signal resolution at low toxin concentrations (with most of the incident light blocked) for the competitive assay. By monitoring the I(DS) of the FET whose gate is driven by the V(OC), quantitative detection of Aflatoxin B1 has been achieved in the range of 0-15ppb. 相似文献
93.
Fujii R Minami A Tsukagoshi T Sato N Sahara T Ohgiya S Gomi K Oikawa H 《Bioscience, biotechnology, and biochemistry》2011,75(9):1813-1817
Clustering of biosynthetic genes for producing fungal secondary metabolites, which frequently consist of less than ten genes, has been recognized with numerous genomes. The heterologous expression of whole genes in the clusters will therefore produce various types of natural products when using a suitable fungal host. We introduced the whole gene cluster for the biosynthesis of diterpene aphidicolin into the fungal quadruple auxotrophic host, Aspergillus oryzae, by using four different vectors (pTAex3, pPTRI, pUSA and pAdeA) which harbor a starch-inducible promoter/terminator to examine the expression conditions. The resulting quadruple transformant carrying the genes of geranylgeranyl diphosphate synthase PbGGS, terpene synthase PbACS, and two monooxygenases (PbP450-1 and PbP450-2) produced aphidicolin. The double and triple transformants also respectively produced aphidicolan-16β-ol and 3-deoxyaphidicolin. Alternative host Saccharomyces cerevisiae carrying the genes, PbGGS and PbACS, produced key intermediate aphidicolan-16β-ol. This is the first example of a total biosynthesis of terpenoids using fungal hosts. 相似文献
94.
95.
Fe-Lin Lin Wu Yu-Fen Liang Yuan-Chen Chang Hao-Hsin Yo Ming-Feng Wei Li-Jiuan Shen 《Journal of biomedical science》2011,18(1):25
Background
Sensitivity of cancer cells to recombinant arginine deiminase (rADI) depends on expression of argininosuccinate synthetase (AS), a rate-limiting enzyme in synthesis of arginine from citrulline. To understand the efficiency of RNA interfering of AS in sensitizing the resistant cancer cells to rADI, the down regulation of AS transiently and permanently were performed in vitro, respectively. 相似文献96.
Mycobacteriosis, caused by the intracellular parasitism Mycobacterium sp., causes economic damages to aquaculture production in Japan, particularly in seriola fish production. Antibiotics are not effective against Mycobacterium sp. and so a potent vaccine is needed. We previously reported that BCG vaccine (Mycobacterium bovis BCG) induces adaptive immunity against Mycobacterium sp. in Japanese flounder, Paralichthys olivaceus. In a phylogenetic tree, the genes for a major antigen, the Ag85 complex, in Mycobacterium sp. TUMSAT-Msp001 are closely related to homologues in Mycobacterium ulcerans. M. bovis BCG was detected until 7 days post-injection at the injection site (muscle) and 28 days post-vaccination in spleen. Cumulative mortality of amberjack, Seriola dumerili vaccinated intramuscularly (i.m.) and intraperitoneally (i.p.) with M. bovis BCG was 32.3% and 59.5% respectively, at 24 days post-infection of Mycobacterium sp., compared to 97.8% in PBS-injected fish. The bacterial counts of Mycobacterium sp. in spleen of both i.m.-and i.p.-vaccinated fish (6.2 × 103 and 1.3 × 104 CFU/mg tissue, respectively) at 20 days post-infection were significantly lower (P < 0.01) than those of PBS-injected fish (8.0 × 106 CFU/mg). Furthermore, Immersion challenge with Mycobacterium sp. TUMSAT Msp-001 showed 50% RPS value in BCG i.m.-vaccinated fish at the end of the experiment. These results support our previous study using Japanese flounder and suggest that BCG vaccine is also effective against Mycobacterium sp. infection in amberjack. 相似文献
97.
Y Kuwahara T Oikawa Y Ochiai M H Roudkenar M Fukumoto T Shimura Y Ohtake Y Ohkubo S Mori Y Uchiyama M Fukumoto 《Cell death & disease》2011,2(6):e177
Radiotherapy is a well-established treatment for cancer. However, the existence of radioresistant cells is one of the major obstacles in radiotherapy. In order to understand the mechanism of cellular radioresistance and develop more effective radiotherapy, we have established clinically relevant radioresistant (CRR) cell lines, which continue to proliferate under daily exposure to 2 Gray (Gy) of X-rays for >30 days. X-ray irradiation significantly induced autophagic cells in parental cells, which was exiguous in CRR cells, suggesting that autophagic cell death is involved in cellular radiosensitivity. An autophagy inducer, rapamycin sensitized CRR cells to the level of parental cells and suppressed cell growth. An autophagy inhibitor, 3-methyladenine induced radioresistance of parental cells. Furthermore, inhibition of autophagy by knockdown of Beclin-1 made parental cells radioresistant to acute radiation. These suggest that the suppression of autophagic cell death but not apoptosis is mainly involved in cellular radioresistance. Therefore, the enhancement of autophagy may have a considerable impact on the treatment of radioresistant tumor. 相似文献
98.
Comparative efficacy and immunogenicity of replication-defective, recombinant glycoprotein, and DNA vaccines for herpes simplex virus 2 infections in mice and guinea pigs 总被引:2,自引:0,他引:2 下载免费PDF全文
Hoshino Y Dalai SK Wang K Pesnicak L Lau TY Knipe DM Cohen JI Straus SE 《Journal of virology》2005,79(1):410-418
Many candidate vaccines are effective in animal models of genital herpes simplex virus type 2 (HSV-2) infection. Among them, clinical trials showed moderate protection from genital disease with recombinant HSV-2 glycoprotein D (gD2) in alum-monophosphoryl lipid A adjuvant only in HSV women seronegative for both HSV-1 and HSV-2, encouraging development of additional vaccine options. Therefore, we undertook direct comparative studies of the prophylactic and therapeutic efficacies and immunogenicities of three different classes of candidate vaccines given in four regimens to two species of animals: recombinant gD2, a plasmid expressing gD2, and dl5-29, a replication-defective strain of HSV-2 with the essential genes UL5 and UL29 deleted. Both dl5-29 and gD2 were highly effective in attenuating acute and recurrent disease and reducing latent viral load, and both were superior to the plasmid vaccine alone or the plasmid vaccine followed by one dose of dl5-29. dl5-29 was also effective in treating established infections. Moreover, latent dl5-29 virus could not be detected by PCR in sacral ganglia from guinea pigs vaccinated intravaginally. Finally, dl5-29 was superior to gD2 in inducing higher neutralizing antibody titers and the more rapid accumulation of HSV-2-specific CD8+ T cells in trigeminal ganglia after challenge with wild-type virus. Given its efficacy, its defectiveness for latency, and its ability to induce rapid, virus-specific CD8(+)-T-cell responses, the dl5-29 vaccine may be a good candidate for early-phase human trials. 相似文献
99.
Input of orexin/hypocretin neurons revealed by a genetically encoded tracer in mice 总被引:10,自引:0,他引:10
Sakurai T Nagata R Yamanaka A Kawamura H Tsujino N Muraki Y Kageyama H Kunita S Takahashi S Goto K Koyama Y Shioda S Yanagisawa M 《Neuron》2005,46(2):297-308
The finding of orexin/hypocretin deficiency in narcolepsy patients suggests that this hypothalamic neuropeptide plays a crucial role in regulating sleep/wakefulness states. However, very little is known about the synaptic input of orexin/hypocretin-producing neurons (orexin neurons). We applied a transgenic method to map upstream neuronal populations that have synaptic connections to orexin neurons and revealed that orexin neurons receive input from several brain areas. These include the amygdala, basal forebrain cholinergic neurons, GABAergic neurons in the preoptic area, and serotonergic neurons in the median/paramedian raphe nuclei. Monoamine-containing groups that are innervated by orexin neurons do not receive reciprocal connections, while cholinergic neurons in the basal forebrain have reciprocal connections, which might be important for consolidating wakefulness. Electrophysiological study showed that carbachol excites almost one-third of orexin neurons and inhibits a small population of orexin neurons. These neuroanatomical findings provide important insights into the neural pathways that regulate sleep/wakefulness states. 相似文献
100.