全文获取类型
收费全文 | 6840篇 |
免费 | 205篇 |
国内免费 | 248篇 |
专业分类
7293篇 |
出版年
2024年 | 10篇 |
2023年 | 44篇 |
2022年 | 86篇 |
2021年 | 113篇 |
2020年 | 94篇 |
2019年 | 159篇 |
2018年 | 204篇 |
2017年 | 91篇 |
2016年 | 109篇 |
2015年 | 153篇 |
2014年 | 373篇 |
2013年 | 468篇 |
2012年 | 259篇 |
2011年 | 402篇 |
2010年 | 230篇 |
2009年 | 353篇 |
2008年 | 387篇 |
2007年 | 363篇 |
2006年 | 371篇 |
2005年 | 376篇 |
2004年 | 322篇 |
2003年 | 284篇 |
2002年 | 240篇 |
2001年 | 150篇 |
2000年 | 161篇 |
1999年 | 171篇 |
1998年 | 156篇 |
1997年 | 147篇 |
1996年 | 124篇 |
1995年 | 132篇 |
1994年 | 95篇 |
1993年 | 70篇 |
1992年 | 75篇 |
1991年 | 62篇 |
1990年 | 56篇 |
1989年 | 50篇 |
1988年 | 57篇 |
1987年 | 45篇 |
1986年 | 35篇 |
1985年 | 47篇 |
1984年 | 41篇 |
1983年 | 28篇 |
1982年 | 17篇 |
1981年 | 17篇 |
1980年 | 18篇 |
1979年 | 14篇 |
1978年 | 7篇 |
1977年 | 9篇 |
1976年 | 11篇 |
1974年 | 3篇 |
排序方式: 共有7293条查询结果,搜索用时 0 毫秒
101.
Jian-Feng LI Robert QI Liang-Hu QU Autar K Mattoo Ning LI 《植物学报(英文版)》2005,47(11):1352-1363
1-Aminocyclopropane-1-carboxylic acid (ACC) synthase (ACS) is the principal enzyme in phytohormone ethylene biosynthesis. Previous studies have shown that the hypervariable C-terminus of ACS is proteolytically processed in vivo. However, the protease responsible for this has not yet been identified. In the present study, we investigated the processing of the 55-kDa full-length tomato ACS (LeACS2) into 52-, 50- and 49-kDa truncated isoforms in ripening tomato (Lycopersicon esculentum Mill. cv. Cooperation 903) fruit using the sodium dodecyl sulfate-boiling method. Meanwhile, an LeACS2-processing protease was purified via multi-step column chromatography from tomato fruit. Subsequent biochemical analysis of the 64-kDa purified protease revealed that it is a metalloprotease active at multiple cleavage sites within the hypervariable C-terminus of LeACS2. N-terminal sequencing and matrix-assisted laser desorption/ionization time-of-flight analysis indicated that the LeACS2-processing metalloprotease cleaves at the C-terminal sites Lys^438, Glu^447, Lys^448, Asn^456, Ser^460, Ser^462, Lys^463, and Leu^474, but does not cleave the N- terminus of LeACS2. Four C-terminus-deleted (26-50 amino acids) LeACS2 fusion proteins were overproduced and subjected to proteolysis by this metalloprotease to identify the multiple cleavage sites located on the N-terminal side of the phosphorylation site Ser^460. The results indisputably confirmed the presence of cleavage sites within the region between the α-helix domain (H14) and Ser^460 for this metalloprotease. Furthermore, the resulting C-terminally truncated LeACS2 isoforms were active enzymatically. Because this protease could produce LeACS2 isoforms in vitro similar to those detected in vivo, it is proposed that this metalloprotease may be involved in the proteolysis of LeACS2 in vivo. 相似文献
102.
Musayev F Sachdeva S Scarsdale JN Reynolds KA Wright HT 《Journal of molecular biology》2005,346(5):1313-1321
Beta-ketoacyl-acyl carrier protein synthase III (FabH) catalyzes a two step reaction that initiates the pathway of fatty acid biosynthesis in plants and bacteria. In Mycobacterium tuberculosis, FabH catalyzes extension of lauroyl, myristoyl and palmitoyl groups from which cell wall mycolic acids of the bacterium are formed. The first step of the reaction is an acyl group transfer from acyl-coenzyme A to the active-site cysteine of the enzyme; the second step is acyl chain extension by two carbon atoms through Claisen condensation with malonyl-acyl carrier protein. We have previously determined the crystal structure of a type II, dissociated M.tuberculosis FabH, which catalyzes extension of lauroyl, myristoyl and palmitoyl groups. Here we describe the first long-chain Michaelis substrate complex of a FabH, that of lauroyl-coenzyme A with a catalytically disabled Cys-->Ala mutant of M.tuberculosis FabH. An elongated channel extending from the mutated active-site cysteine defines the acyl group binding locus that confers unique acyl substrate specificity on M.tuberculosis FabH. CoA lies in a second channel, bound primarily through interactions of its nucleotide group at the enzyme surface. The apparent weak association of CoA in this complex may play a role in the binding and dissociation of long chain acyl-CoA substrates and products and poses questions pertinent to the mechanism of this enzyme. 相似文献
103.
Increasing evidence suggests that an inhibition of the proteasome, as demonstrated in Parkinson's disease, might be involved in Alzheimer's disease. In this disease and other Tauopathies, Tau proteins are hyperphosphorylated and aggregated within degenerating neurons. In this state, Tau is also ubiquitinated, suggesting that the proteasome might be involved in Tau proteolysis. Thus, to investigate if proteasome inhibition leads to accumulation, hyperphosphorylation and aggregation of Tau, we used neuroblastoma cells overexpressing Tau proteins. Surprisingly, we showed that the inhibition of the proteasome led to a bidirectional degradation of Tau. Following this result, the cellular mechanisms that may degrade Tau were investigated. 相似文献
104.
Ethylene regulates entry into several types of plant developmental cell death and senescence programs besides mediating plant responses to biotic and abiotic stress. The response of cereals to conditions of drought includes loss of leaf function and premature onset of senescence in older leaves. In this study, ACC synthase ( ACS ) mutants, affecting the first step in ethylene biosynthesis, were isolated in maize and their effect on leaf function examined. Loss of ZmACS6 expression resulted in delayed leaf senescence under normal growth conditions and inhibited drought-induced senescence. Zmacs6 leaves continued to be photosynthetically active under both conditions indicating that leaf function was maintained. The delayed senescence phenotype associated with loss of ZmACS6 expression was complemented by exogenous ACC. Surprisingly, elevated levels of foliar chlorophyll, Rubisco, and soluble protein as well as improved leaf performance was observed for all Zmasc6 leaves, including young and fully expanded leaves which were far from initiating senescence. These observations suggest that ethylene may serve to regulate leaf performance throughout its lifespan as well as to determine the onset of natural senescence and mediate drought-induced senescence. 相似文献
105.
Upregulation of thromboxane synthase in human colorectal carcinoma and the cancer cell proliferation by thromboxane A2 总被引:2,自引:0,他引:2
Sakai H Suzuki T Takahashi Y Ukai M Tauchi K Fujii T Horikawa N Minamimura T Tabuchi Y Morii M Tsukada K Takeguchi N 《FEBS letters》2006,580(14):3368-3374
Tumor growth of colorectal cancers accompanies upregulation of cyclooxygenase-2, which catalyzes a conversion step from arachidonic acid to prostaglandin H(2) (PGH(2)). Here, we compared the expression levels of thromboxane synthase (TXS), which catalyzes the conversion of PGH(2) to thromboxane A(2) (TXA(2)), between human colorectal cancer tissue and its accompanying normal mucosa. It was found that TXS protein was consistently upregulated in the cancer tissues from different patients. TXS was also highly expressed in human colonic cancer cell lines. Depletion of TXS protein by the antisense oligonucleotide inhibited proliferation of the cancer cells. This inhibition was rescued by the direct addition of a stable analogue of TXA(2). The present results suggest that overexpression of TXS and subsequent excess production of TXA(2) in the cancer cells may be involved in the tumor growth of human colorectum. 相似文献
106.
Aya Nagaoka Hiroyuki Yoshida Sachiko Nakamura Tomohiko Morikawa Keigo Kawabata Masaki Kobayashi Shingo Sakai Yoshito Takahashi Yasunori Okada Shintaro Inoue 《The Journal of biological chemistry》2015,290(52):30910-30923
Regulation of hyaluronan (HA) synthesis and degradation is essential to maintenance of extracellular matrix homeostasis. We recently reported that HYBID (HYaluronan-Binding protein Involved in hyaluronan Depolymerization), also called KIAA1199, plays a key role in HA depolymerization in skin and arthritic synovial fibroblasts. However, regulation of HA metabolism mediated by HYBID and HA synthases (HASs) under stimulation with growth factors remains obscure. Here we report that TGF-β1, basic FGF, EGF, and PDGF-BB commonly enhance total amount of HA in skin fibroblasts through up-regulation of HAS expression, but molecular size of newly produced HA is dependent on HYBID expression levels. Stimulation of HAS1/2 expression and suppression of HYBID expression by TGF-β1 were abrogated by blockade of the MAPK and/or Smad signaling and the PI3K-Akt signaling, respectively. In normal human skin, expression of the TGF-β1 receptors correlated positively with HAS2 expression and inversely with HYBID expression. On the other hand, TGF-β1 up-regulated HAS1/2 expression but exerted only a slight suppressive effect on HYBID expression in synovial fibroblasts from the patients with osteoarthritis or rheumatoid arthritis, resulting in the production of lower molecular weight HA compared with normal skin and synovial fibroblasts. These data demonstrate that although TGF-β1, basic FGF, EGF, and PDGF-BB enhance HA production in skin fibroblasts, TGF-β1 most efficiently contributes to production of high molecular weight HA by HAS up-regulation and HYBID down-regulation and suggests that inefficient down-regulation of HYBID by TGF-β1 in arthritic synovial fibroblasts may be linked to accumulation of depolymerized HA in synovial fluids in arthritis patients. 相似文献
107.
Pus10, a recently identified pseudouridine (Ψ) synthase, does not belong to any of the five commonly identified families of Ψ synthases. Pyrococcus furiosus Pus10 has been shown to produce Ψ55 in tRNAs. However, in vitro studies have identified another mechanism for tRNA Ψ55 production in Archaea, which uses Cbf5 and other core proteins of the H/ACA ribonucleoprotein complex, in a guide RNA-independent manner. Pus10 homologs have been observed in nearly all sequenced archaeal genomes and in some higher eukaryotes, but not in yeast and bacteria. This coincides with the presence of Ψ54 in the tRNAs of Archaea and higher eukaryotes and its absence in yeast and bacteria. No tRNA Ψ54 synthase has been reported so far. Here, using recombinant Methanocaldococcus jannaschii and P. furiosus Pus10, we show that these proteins can function as synthase for both tRNA Ψ54 and Ψ55. The two modifications seem to occur independently. Salt concentration dependent variations in these activities of both proteins are observed. The Ψ54 synthase activity of M. jannaschii protein is robust, while the same activity of P. furiosus protein is weak. Probable reasons for these differences are discussed. Furthermore, unlike bacterial TruB and yeast Pus4, archaeal Pus10 does not require a U54•A58 reverse Hoogstein base pair and pyrimidine at position 56 to convert tRNA U55 to Ψ55. The homology of eukaryal Pus10 with archaeal Pus10 suggests that the former may also have a tRNA Ψ54 synthase activity. 相似文献
108.
C. M. Bishop P. J. Butler N. M. Atkinson 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1995,164(8):618-621
Following extended periods of relative inactivity, or prior to migration, birds are able to increase the aerobic capacity of their locomotory muscles. Thyroid hormones may influence this process. A preliminary study was undertaken to assess the ability of elevated levels of thyroxine to increase the aerobic capacity of the locomotory and cardiac muscles of adult tufted ducks. Administration of thyroxine in the food for 8 weeks had little effect on body mass or on the masses of the pectoralis, semitendinosus and iliofibularis muscles, although there were increases in resting oxygen consumption and in the mass of the cardiac ventricles. The maximum activity of the aerobic enzyme, citrate synthase, was significantly greater in the left ventricle, liver, and iliofibularis muscles (P<0.005) of treated birds. However, while there was clearly no difference in activity in the semimembranosus leg muscle, that of the pectoralis was not quite significant (P=0.078). It is concluded that addition of supra-physiological levels of exogenous thyroxine may induce a differential increase in the maximum activity of citrate synthase in the locomotor muscles of the tufted duck, which is correlated with the fibre type composition of these muscles. These results are consistent with those found in studies on rats, with slow oxidative fibres being the most sensitive, and fast glycolytic fibres the least sensitive, to thyroxine treatment.Abbreviations BM
body mass
- CS
citrate synthase
- CYTOX
cytochrome c oxidase
- FG
last glycolytic
- FOG
fast oxydative glycolytic
-
VO2
oxygen consumption
- SO
slow oxidative
- T4
thyroxine
- T3
triiodothyronine 相似文献
109.
Polyamine metabolism and its regulation 总被引:20,自引:1,他引:20
Antonio F. Tiburcio Teresa Altabella Antoni Borrell Carles Masgrau 《Physiologia plantarum》1997,100(3):664-674
110.
The biosynthesis of ethylene was examined in suspension-cultured cells of parsley (Petroselinum hortense) treated with an elicitor from cell walls of Phytophthora megasperma. Untreated cells contained 50 nmol g-1 of the ethylene precursor, 1-aminocyclopropane-1-carboxylic acid (ACC), and produced ethylene at a rate of about 0.5 nmol g-1 h-1. Within 2 h after addition of elicitor to the culture medium, the cells started to produce more ethylene and accumulated more ACC. Exogenously added ACC did not increase the rate of ethylene production in control or elicitor-treated cells, indicating that the enzyme converting ACC to ethylene was limiting in both cases. The first enzyme in ethylene biosynthesis, ACC synthase, was very rapidly and transiently induced by the elicitor treatment. Its activity increased more than tenfold within 60 min. Density labelling with 2H2O showed that this increase was caused by the denovo synthesis of the enzyme protein. Cordycepin and actinomycin D did not affect the induction of ACC synthase, indicating that the synthesis of new mRNA was not required. The peak of ACC-synthase activity preceded the maximal phenylalanine ammonia-lyase (PAL) activity by several hours. Exogenously supplied ethylene or ACC did not induce PAL. However, aminoethoxyvinylglycine, an inhibitor of ACC synthase, suppressed the rise in ethylene production in elicitor-treated cells and partially inhibited the induction of PAL. Exogenously supplied ACC reversed this inhibition. It is concluded that induction of the ethylene biosynthetic pathway is a very early symptom of elicitor action. Although ethylene alone is not a sufficient signal for PAL induction, the enhanced activity of ACC synthase and the ethylene biosynthetic pathway may be important for the subsequent induction of PAL.Abbreviations ACC
1-aminocyclopropane-1-carboxylic acid
- AVG
aminoethoxyvinylglycine
- PAL
phenylalanine ammonia-lyase 相似文献