全文获取类型
收费全文 | 1222篇 |
免费 | 78篇 |
国内免费 | 1篇 |
出版年
2022年 | 6篇 |
2021年 | 24篇 |
2020年 | 21篇 |
2019年 | 19篇 |
2018年 | 27篇 |
2017年 | 16篇 |
2016年 | 24篇 |
2015年 | 46篇 |
2014年 | 55篇 |
2013年 | 76篇 |
2012年 | 84篇 |
2011年 | 75篇 |
2010年 | 38篇 |
2009年 | 38篇 |
2008年 | 77篇 |
2007年 | 67篇 |
2006年 | 49篇 |
2005年 | 51篇 |
2004年 | 53篇 |
2003年 | 59篇 |
2002年 | 50篇 |
2001年 | 39篇 |
2000年 | 33篇 |
1999年 | 31篇 |
1998年 | 22篇 |
1997年 | 6篇 |
1996年 | 10篇 |
1995年 | 9篇 |
1994年 | 10篇 |
1993年 | 8篇 |
1992年 | 21篇 |
1991年 | 28篇 |
1990年 | 16篇 |
1989年 | 16篇 |
1988年 | 17篇 |
1987年 | 8篇 |
1986年 | 9篇 |
1985年 | 10篇 |
1984年 | 6篇 |
1983年 | 7篇 |
1982年 | 6篇 |
1981年 | 3篇 |
1980年 | 6篇 |
1979年 | 3篇 |
1975年 | 4篇 |
1974年 | 2篇 |
1972年 | 2篇 |
1970年 | 2篇 |
1968年 | 3篇 |
1967年 | 2篇 |
排序方式: 共有1301条查询结果,搜索用时 265 毫秒
121.
An efficient process for the production of fuel ethanol from bamboo that consisted of hydrolysis with concentrated sulfuric acid, removal of color compounds, separation of acid and sugar, hydrolysis of oligosaccharides and subsequent continuous ethanol fermentation was developed. The highest sugar recovery efficiency was 81.6% when concentrated sulfuric acid hydrolysis was carried out under the optimum conditions. Continuous separation of acid from the saccharified liquid after removal of color compounds with activated carbon was conducted using an improved simulated moving bed (ISMB) system, and 98.4% of sugar and 90.5% of acid were recovered. After oligosaccharide hydrolysis and pH adjustment, the unsterilized saccharified liquid was subjected to continuous ethanol fermentation using Saccharomycescerevisiae strain KF-7. The ethanol concentration, the fermentation yield based on glucose and the ethanol productivity were approximately 27.2 g/l, 92.0% and 8.2 g/l/h, respectively. These results suggest that the process is effective for production of fuel ethanol from bamboo. 相似文献
122.
N-Methylimidazolium chloride is found to catalyze a coupling reaction between monophosphates and activated phosphorous-nitrogen intermediates such as a phosphorimidazolide and phosphoromorpholidate to form biologically important unsymmetrical pyrophosphate diesters. The catalyst is much more active, cheaper, and less explosive than 1H-tetrazole, known as the best catalyst for the pyrophosphate formation over a decade. The mild and neutral reaction conditions are compatible with allylic pyrophosphate formation in Lipid I syntheisis. 31P NMR experiments suggest that the catalyst acts not only as an acid but also as a nucleophile to form cationic and electrophilic phosphor-N-methylimidazolide intermediates in the pyrophosphate formation. 相似文献
123.
Yamazaki D Tabara Y Kita S Hanada H Komazaki S Naitou D Mishima A Nishi M Yamamura H Yamamoto S Kakizawa S Miyachi H Yamamoto S Miyata T Kawano Y Kamide K Ogihara T Hata A Umemura S Soma M Takahashi N Imaizumi Y Miki T Iwamoto T Takeshima H 《Cell metabolism》2011,14(2):231-241
TRIC channel subtypes, namely TRIC-A and TRIC-B, are intracellular monovalent cation channels postulated to mediate counter-ion movements facilitating physiological Ca(2+) release from internal stores. Tric-a-knockout mice developed hypertension during the daytime due to enhanced myogenic tone in resistance arteries. There are two Ca(2+) release mechanisms in vascular smooth muscle cells (VSMCs); incidental opening of ryanodine receptors (RyRs) generates local Ca(2+) sparks to induce hyperpolarization, while agonist-induced activation of inositol trisphosphate receptors (IP(3)Rs) evokes global Ca(2+) transients causing contraction. Tric-a gene ablation inhibited RyR-mediated hyperpolarization signaling to stimulate voltage-dependent Ca(2+) influx, and adversely enhanced IP(3)R-mediated Ca(2+) transients by overloading Ca(2+) stores in VSMCs. Moreover, association analysis identified single-nucleotide polymorphisms (SNPs) around the human TRIC-A gene that increase hypertension risk and restrict the efficiency of antihypertensive drugs. Therefore, TRIC-A channels contribute to maintaining blood pressure, while TRIC-A SNPs could provide biomarkers for constitutional diagnosis and personalized medical treatment of essential hypertension. 相似文献
124.
Starvation induced cell death in autophagy-defective yeast mutants is caused by mitochondria dysfunction 总被引:1,自引:0,他引:1
Autophagy is a highly-conserved cellular degradation and recycling system that is essential for cell survival during nutrient starvation. The loss of viability had been used as an initial screen to identify autophagy-defective (atg) mutants of the yeast Saccharomyces cerevisiae, but the mechanism of cell death in these mutants has remained unclear. When cells grown in a rich medium were transferred to a synthetic nitrogen starvation media, secreted metabolites lowered the extracellular pH below 3.0 and autophagy-defective mutants mostly died. We found that buffering of the starvation medium dramatically restored the viability of atg mutants. In response to starvation, wild-type (WT) cells were able to upregulate components of the respiratory pathway and ROS (reactive oxygen species) scavenging enzymes, but atg mutants lacked this synthetic capacity. Consequently, autophagy-defective mutants accumulated the high level of ROS, leading to deficient respiratory function, resulting in the loss of mitochondria DNA (mtDNA). We also showed that mtDNA deficient cells are subject to cell death under low pH starvation conditions. Taken together, under starvation conditions non-selective autophagy, rather than mitophagy, plays an essential role in preventing ROS accumulation, and thus in maintaining mitochondria function. The failure of response to starvation is the major cause of cell death in atg mutants. 相似文献
125.
126.
Kubo A Stull R Takeuchi M Bonham K Gouon-Evans V Sho M Iwano M Saito Y Keller G Snodgrass R 《PloS one》2011,6(9):e24058
In order to define the molecular mechanisms regulating the specification and differentiation of pancreatic β-islet cells, we investigated the effect of upregulating Pdx1 and Ngn3 during the differentiation of the β-islet-like cells from murine embryonic stem (ES) cell-derived activin induced-endoderm. Induced overexpression of Pdx1 resulted in a significant upregulation of insulin (Ins1 and Ins2), and other pancreas-related genes. To enhance the developmental progression from the pancreatic bud to the formation of the endocrine lineages, we induced the overexpression express of Ngn3 together with Pdx1. This combination dramatically increased the level and timing of maximal Ins1 mRNA expression to approximately 100% of that found in the βTC6 insulinoma cell line. Insulin protein and C-peptide expression was confirmed by immunohistochemistry staining. These inductive effects were restricted to c-kit(+) endoderm enriched EB-derived populations suggesting that Pdx1/Ngn3 functions after the specification of pancreatic endoderm. Although insulin secretion was stimulated by various insulin secretagogues, these cells had only limited glucose response. Microarray analysis was used to evaluate the expression of a broad spectrum of pancreatic endocrine cell-related genes as well as genes associated with glucose responses. Taken together, these findings demonstrate the utility of manipulating Pdx1 and Ngn3 expression in a stage-specific manner as an important new strategy for the efficient generation of functionally immature insulin-producing β-islet cells from ES cells. 相似文献
127.
Orihara K Yamazaki T Shinkyo R Sakaki T Inouye K Tsukamoto A Sugiura J Shishido K 《Applied microbiology and biotechnology》2005,69(1):22-28
Rat cytochrome P450, CYP1A1, has been reported to play an important role in the metabolism of mono-trichlorodibenzo-p-dioxins (M-TriCDDs). To breed lignin (and M-TetraCDDs)-degrading basidiomycete Coriolus hirsutus strains producing rat CYP1A1, an expression cassette [C. hirsutus gpd promoter-C. hirsutus gpd 5′ portion (224-bp of 1st exon–8th base of 4th exon)-rat cyp1a1 cDNA-Lentinula edodes priA terminator] was constructed and inserted into pUCR1 carrying the C. hirsutus arg1 gene. The resulting recombinant plasmid, MIp5-(cyp1a1 + arg1) was introduced into protoplasts of C. hirsutus monokaryotic strain OJ1078 (Arg−, Leu−), obtaining three good Arg+ transformants. These transformants [ChTF5-2(CYP1A1), ChTF5-4(CYP1A1), and ChTF5-6(CYP1A1)] were estimated to carry nine, six, and seven copies of the expression cassette on their chromosomes, respectively. Immunoblot analysis revealed that the three transformants produce similar amounts of rat CYP1A1 enzyme. ChTF5-2(CYP1A1), ChTF5-4(CYP1A1), ChTF5-6(CYP1A1) and recipient OJ1078 were cultivated in a liquid medium containing 2,7/2,8(at a ratio of 1:1)-dichlorodibenzo-p-dioxins (2,7/2,8-DCDDs) and the amount of intra- and extracellular 2,7/2,8-DCDDs remaining was measured. The results showed that all three transformants efficiently transform 2,7/2,8-DCDDs through the action of the recombinant rat CYP1A1 enzyme. 相似文献
128.
Unprecedented intraspecific diversity of the MHC class I region of a teleost medaka, Oryzias latipes
Tsukamoto K Hayashi S Matsuo MY Nonaka MI Kondo M Shima A Asakawa S Shimizu N Nonaka M 《Immunogenetics》2005,57(6):420-431
The major histocompatibility complex (MHC) is present at a single chromosomal locus of all jawed vertebrate analyzed so far,
from sharks to mammals, except for teleosts whose orthologs of the mammalian MHC-encoded genes are dispersed at several chromosomal
loci. Even in teleosts, several class IA genes and those genes directly involved in class I antigen presentation preserve
their linkage, defining the teleost MHC class I region. We determined the complete nucleotide sequence of the MHC class I
region of the inbred HNI strain of medaka, Oryzias latipes (northern Japan population-derived), from four overlapping bacterial artificial chromosome (BAC) clones spanning 540,982 bp,
and compared it with the published sequence of the corresponding region of the inbred Hd-rR strain of medaka (425,935 bp,
southern Japan population-derived) as the first extensive study of intraspecies polymorphisms of the ectotherm MHC regions.
A segment of about 100 kb in the middle of the compared sequences encompassing two class Ia genes and two immunoproteasome
subunit genes, PSMB8 and PSMB10, was so divergent between these two inbred strains that a reliable sequence alignment could not be made. The rest of the
compared region (about 320 kb) showed a fair correspondence, and an approximately 96% nucleotide identity was observed upon
gap-free segmental alignment. These results indicate that the medaka MHC class I region contains an ∼100-kb polymorphic core,
which is most probably evolving adaptively by accumulation of point mutations and extensive genetic rearrangements such as
insertions, deletions and duplications.
The nucleotide sequence data of HNI MHC class I region reported in this paper have been submitted to the DDBJ/EMBL/GenBank
and were assigned the accession number AB183488. 相似文献
129.
Control of mRNA translation preserves endoplasmic reticulum function in beta cells and maintains glucose homeostasis 总被引:18,自引:0,他引:18
Scheuner D Vander Mierde D Song B Flamez D Creemers JW Tsukamoto K Ribick M Schuit FC Kaufman RJ 《Nature medicine》2005,11(7):757-764
Type 2 diabetes is a disorder of hyperglycemia resulting from failure of beta cells to produce adequate insulin to accommodate an increased metabolic demand. Here we show that regulation of mRNA translation through phosphorylation of eukaryotic initiation factor 2 (eIF2alpha) is essential to preserve the integrity of the endoplasmic reticulum (ER) and to increase insulin production to meet the demand imposed by a high-fat diet. Accumulation of unfolded proteins in the ER activates phosphorylation of eIF2alpha at Ser51 and inhibits translation. To elucidate the role of this pathway in beta-cell function we studied glucose homeostasis in Eif2s1(tm1Rjk) mutant mice, which have an alanine substitution at Ser51. Heterozygous (Eif2s1(+/tm1Rjk)) mice became obese and diabetic on a high-fat diet. Profound glucose intolerance resulted from reduced insulin secretion accompanied by abnormal distension of the ER lumen, defective trafficking of proinsulin, and a reduced number of insulin granules in beta cells. We propose that translational control couples insulin synthesis with folding capacity to maintain ER integrity and that this signal is essential to prevent diet-induced type 2 diabetes. 相似文献
130.
Role of Helicobacter pylori in gastric carcinogenesis: the origin of gastric cancers and heterotopic proliferative glands in Mongolian gerbils 总被引:7,自引:0,他引:7
Helicobacter pylori infection is well accepted to be a very important factor for the development of gastric carcinogenesis in the human stomach. In Mongolian gerbils treated with chemical carcinogens, H. pylori infection enhances glandular stomach carcinogenesis, and eradication of infection and results in curtailment of enhancing effects, particularly at early stages of associated inflammation. A high-salt diet exacerbates the effects of H. pylori infection on gastric carcinogenesis, and these two factors act synergistically to promote the development of gastric cancers in this animal model. However, the bacterium exerts the greater effects. Early acquisition significantly increases gastric chemical carcinogenesis in Mongolian gerbils, as compared to later infection. While heterotopic proliferative glands, hyperplastic and dilated glands localized beneath the muscularis mucosae, frequently develop with H. pylori infection alone in this animal model, they obviously regress on eradication, suggesting a relation to severe gastritis, rather than a malignant character. Furthermore, endocrine cells, positive for chromogranin A, are observed in the heterotopic proliferative glands, in contrast to cancerous lesions which lack endocrine elements. In conclusion, H. pylori is not an initiator, but rather a strong promoter of gastric carcinogenesis, whose eradication, together with reduction in salt intake, might effectively prevent gastric cancer development. 相似文献