全文获取类型
收费全文 | 4451篇 |
免费 | 245篇 |
出版年
2023年 | 18篇 |
2022年 | 34篇 |
2021年 | 72篇 |
2020年 | 51篇 |
2019年 | 59篇 |
2018年 | 85篇 |
2017年 | 87篇 |
2016年 | 126篇 |
2015年 | 175篇 |
2014年 | 181篇 |
2013年 | 311篇 |
2012年 | 310篇 |
2011年 | 303篇 |
2010年 | 206篇 |
2009年 | 168篇 |
2008年 | 319篇 |
2007年 | 263篇 |
2006年 | 281篇 |
2005年 | 261篇 |
2004年 | 210篇 |
2003年 | 219篇 |
2002年 | 166篇 |
2001年 | 60篇 |
2000年 | 75篇 |
1999年 | 68篇 |
1998年 | 26篇 |
1997年 | 29篇 |
1996年 | 29篇 |
1995年 | 30篇 |
1994年 | 10篇 |
1993年 | 18篇 |
1992年 | 46篇 |
1991年 | 38篇 |
1990年 | 28篇 |
1989年 | 33篇 |
1988年 | 26篇 |
1987年 | 30篇 |
1986年 | 24篇 |
1985年 | 22篇 |
1984年 | 21篇 |
1983年 | 16篇 |
1982年 | 11篇 |
1981年 | 10篇 |
1980年 | 13篇 |
1979年 | 13篇 |
1977年 | 14篇 |
1976年 | 12篇 |
1975年 | 11篇 |
1974年 | 16篇 |
1972年 | 14篇 |
排序方式: 共有4696条查询结果,搜索用时 390 毫秒
131.
Atsuyoshi Nishina Hirokazu Kimura Hiroyuki Tsukagoshi Kunihisa Kozawa Mamoru Koketsu Masayuki Ninomiya Daisuke Sato Yutaro Obara Shoei Furukawa 《Neurochemical research》2013,38(11):2397-2407
The cellular effects of eleven compounds including chalcone glycosides isolated from Brassica rapa L. ‘hidabeni’ and their synthetic derivatives were studied in rat pheochromocytoma PC12 cells. Of the compounds tested, 4′-O-β-d-glucopyranosyl-3′,4-dimethoxychalcone (A2) significantly increased the levels of the phosphorylated forms of extracellular signal-regulated kinases 1/2 (ERK 1/2), p38 mitogen-activated protein kinase (p38MAPK), and stress-activated protein kinases/Jun amino-terminal kinases (JNK/SAPK), but it did not affect Akt. Nerve growth factor (NGF), a well-known neurotrophic factor, increased the levels of phosphorylated ERK1/2, JNK/SAPK, and Akt but not p38MAPK, which may mediate marked neurite outgrowth. Signals evoked by A2 shared common characteristics with those induced by NGF; therefore, we evaluated the neuritogenic activity of A2 and found it induced only weak neurite outgrowth. However, this effect was enhanced by pre-treatment with a p38MAPK inhibitor, suggesting that the phosphorylation of p38MAPK down-regulated neurite outgrowth. From the results of this study, it was found that A2 in combination with a p38MAPK inhibitor can induce NGF-like effects. Hence, a combination of chalcone glycosides containing A2 and a p38MAPK inhibitor increases the likelihood that chalcone glycosides could be put to practical use in the form of drugs or alternative medicines to maintain neural health. 相似文献
132.
Rika Kamei Mana Miyakoda Takahiko Tamura Daisuke Kimura Kiri Honma Kazumi Kimura Katsuyuki Yui 《Microbiology and immunology》2013,57(3):213-223
133.
Rice Resistance to Planthoppers and Leafhoppers 总被引:3,自引:0,他引:3
For over 50 years, host-plant resistance has been regarded as an efficient method to reduce yield losses to rice caused by delphacid and cicadelid hoppers. Already a number of resistant rice varieties have been developed and deployed throughout Asia. To date, over 70 hopper resistance genes have been identified in rice; however, less than 10 genes have been deliberately introduced to commercial rice varieties. Currently, due to recent brown planthopper (Nilaparvata lugens [Stål]) and whitebacked planthopper (Sogatella furcifera [Horvath]) outbreaks occurring at an unprecedented scale, researchers are working toward a second generation of resistant varieties using newly identified gene loci and applying new molecular breeding methods. This paper reviews advances in the identification of resistance genes and QTLs against hoppers in rice. It collates all published information on resistance loci and QTLs against the major rice planthoppers and leafhoppers and presents information on gene locations, genetic markers, differential varieties, and wild rice species as sources of resistance. The review indicates that, whereas progress in the identification of genes has been rapid, considerable tidying of the information is required, especially regarding gene nomenclature and resistance spectra. Furthermore, sound information on gene functioning is almost completely lacking. However, hopper responses to resistance mechanisms are likely to be similar because a single phenotyping technique has been applied by most national and international breeding programs during germplasm screening. The review classifies genes occurring at two chromosome regions associated with several identified resistance loci and highlights these (Chr4S: BphR-R and Chr12L: BphR-R) as general stress response regions. The review calls for a greater diversity of phenotyping methods to enhance the durability of resistant varieties developed using marker-aided selection and emphasizes a need to anticipate the development of virulent hopper populations in response to the field deployment of genes. 相似文献
134.
OsTZF1, a CCCH-Tandem Zinc Finger Protein,Confers Delayed Senescence and Stress Tolerance in Rice by Regulating Stress-Related Genes 总被引:1,自引:0,他引:1
135.
Rizky Abdulah Herlambang Noerjasin Leri Septiani Mutakin Irma R. Defi Eka W. Suradji Irma M. Puspitasari Melisa I. Barliana Chiho Yamazaki Minato Nakazawa Hiroshi Koyama 《Biological trace element research》2013,154(1):1-6
Selenium is an essential nutrient for human health, and maternal selenium concentration has been reported to be associated with pregnancy outcome. To further investigate the possible role of selenium (Se) in miscarriage, we conducted a case–control study to evaluate the correlations among selenium status, glutathione peroxidase activity, and spontaneous abortion. A total of 46 subjects with normal pregnancies and 25 subjects with spontaneous abortion were recruited, and their serum selenium concentrations and serum glutathione peroxidase activities were analyzed. The total serum selenium concentrations in subjects with normal pregnancies were significantly higher than those of subjects with spontaneous abortion; however, the glutathione peroxidase activities were similar in both groups. We further separated the subjects into smoking and nonsmoking groups, and the logistic regression analysis suggested that total serum selenium concentration, but not serum glutathione peroxidase activity or smoking, was significantly correlated with the incidence of miscarriage. The present study thus reaffirms that low serum selenium levels are associated with miscarriage and that selenium plays an important role in pregnancy maintenance. 相似文献
136.
Hiroaki Tanaka Ken-ichi Akagi Chitose Oneyama Masakazu Tanaka Yuichi Sasaki Takashi Kanou Young-Ho Lee Daisuke Yokogawa Marc-Werner Dobenecker Atsushi Nakagawa Masato Okada Takahisa Ikegami 《The Journal of biological chemistry》2013,288(21):15240-15254
Proteins with Src homology 2 (SH2) domains play major roles in tyrosine kinase signaling. Structures of many SH2 domains have been studied, and the regions involved in their interactions with ligands have been elucidated. However, these analyses have been performed using short peptides consisting of phosphotyrosine followed by a few amino acids, which are described as the canonical recognition sites. Here, we report the solution structure of the SH2 domain of C-terminal Src kinase (Csk) in complex with a longer phosphopeptide from the Csk-binding protein (Cbp). This structure, together with biochemical experiments, revealed the existence of a novel binding region in addition to the canonical phosphotyrosine 314-binding site of Cbp. Mutational analysis of this second region in cells showed that both canonical and novel binding sites are required for tumor suppression through the Cbp-Csk interaction. Furthermore, the data indicate an allosteric connection between Cbp binding and Csk activation that arises from residues in the βB/βC loop of the SH2 domain. 相似文献
137.
Masato Ikeda Aya Miyamoto Sumire Mutoh Yuko Kitano Mei Tajima Daisuke Shirakura Manami Takasaki Satoshi Mitsuhashi Seiki Takeno 《Applied and environmental microbiology》2013,79(15):4586-4594
To develop the infrastructure for biotin production through naturally biotin-auxotrophic Corynebacterium glutamicum, we attempted to engineer the organism into a biotin prototroph and a biotin hyperauxotroph. To confer biotin prototrophy on the organism, the cotranscribed bioBF genes of Escherichia coli were introduced into the C. glutamicum genome, which originally lacked the bioF gene. The resulting strain still required biotin for growth, but it could be replaced by exogenous pimelic acid, a source of the biotin precursor pimelate thioester linked to either coenzyme A (CoA) or acyl carrier protein (ACP). To bridge the gap between the pimelate thioester and its dedicated precursor acyl-CoA (or -ACP), the bioI gene of Bacillus subtilis, which encoded a P450 protein that cleaves a carbon-carbon bond of an acyl-ACP to generate pimeloyl-ACP, was further expressed in the engineered strain by using a plasmid system. This resulted in a biotin prototroph that is capable of the de novo synthesis of biotin. On the other hand, the bioY gene responsible for biotin uptake was disrupted in wild-type C. glutamicum. Whereas the wild-type strain required approximately 1 μg of biotin per liter for normal growth, the bioY disruptant (ΔbioY) required approximately 1 mg of biotin per liter, almost 3 orders of magnitude higher than the wild-type level. The ΔbioY strain showed a similar high requirement for the precursor dethiobiotin, a substrate for bioB-encoded biotin synthase. To eliminate the dependency on dethiobiotin, the bioB gene was further disrupted in both the wild-type strain and the ΔbioY strain. By selectively using the resulting two strains (ΔbioB and ΔbioBY) as indicator strains, we developed a practical biotin bioassay system that can quantify biotin in the seven-digit range, from approximately 0.1 μg to 1 g per liter. This bioassay proved that the engineered biotin prototroph of C. glutamicum produced biotin directly from glucose, albeit at a marginally detectable level (approximately 0.3 μg per liter). 相似文献
138.
139.
Kotaro Ito Yoshiki Hanya Yasuji Koyama 《Applied microbiology and biotechnology》2013,97(19):8581-8590
Glutaminase, an enzyme that hydrolyzes l-glutamine to l-glutamate, plays an important role in the production of fermented foods by enhancing the umami taste. In this study, we found ten glutaminase genes in the Aspergillus sojae genome by conducting a BLAST search of the characterized glutaminase sequence. We subsequently constructed glutaminase gene disruptants. The glutaminase activity of the gahB disruptant was decreased by approximately 90 % in A. sojae and Aspergillus oryzae, indicating that this enzyme (GahB) accounted for the majority of the glutaminase activity in Aspergillus species. Subsequently, GahB protein was purified from the AsgahB-overexpressing transformant and characterized. The molecular mass was estimated to be approximately 110 and 259 kDa by SDS-PAGE and gel filtration chromatography, respectively, indicating that the native form of AsGahB was a dimer. The optimal pH was 9.0, and the optimal temperature was 50 °C. Analysis of substrate specificity revealed that AsGahB had peptidoglutaminase-asparaginase activity, similar to AsGahA, but preferred free l-glutamine to free l-asparagine, C-terminal glutaminyl, and asparaginyl residues in peptides. 相似文献
140.
Ayano Kobayashi Daisuke Sano Jun Hatori Satoshi Ishii Satoshi Okabe 《Applied microbiology and biotechnology》2013,97(16):7427-7437
Bacteroides–Prevotella group is one of the most promising targets for detecting fecal contamination in water environments, principally due to its host-specific distributions and high concentrations in feces of warm-blooded animals. We developed real-time PCR assays for quantifying chicken/duck-, chicken-, and duck-associated Bacteroides–Prevotella 16S rRNA genetic markers (Chicken/Duck-Bac, Chicken-Bac, and Duck-Bac). A reference collection of DNA extracts from 143 individual fecal samples and wastewater treatment plant influent was tested by the newly established markers. The quantification limits of Chicken/Duck-Bac, Chicken-Bac, and Duck-Bac markers in environmental water were 54, 57, and 12 copies/reaction, respectively. It was possible to detect possible fecal contaminations from wild ducks in environmental water with the constructed genetic marker assays, even though the density of total coliforms in the identical water samples was below the detection limit. Chicken/Duck-Bac marker was amplified from feces of wild duck and chicken with the positive ratio of 96 and 61 %, respectively, and no cross-reaction was observed for the other animal feces. Chicken-Bac marker was detected from 70 % of chicken feces, while detected from 39 % of cow feces, 8.3 % of pig feces, and 12 % of swan feces. Duck-Bac marker was detected from 85 % of wild duck feces and cross-reacted with 31 % of cow feces. These levels of detection specificity are common in avian-associated genetic markers previously proposed, which implies that there is a practical limitation in the independent application of avian-associated Bacteroides–Prevotella 16S rRNA genetic markers and a combination with other fecal contamination markers is preferable for detecting fecal contamination in water environments. 相似文献