全文获取类型
收费全文 | 5739篇 |
免费 | 451篇 |
国内免费 | 2篇 |
出版年
2022年 | 26篇 |
2021年 | 61篇 |
2020年 | 33篇 |
2019年 | 39篇 |
2018年 | 58篇 |
2017年 | 66篇 |
2016年 | 105篇 |
2015年 | 133篇 |
2014年 | 187篇 |
2013年 | 272篇 |
2012年 | 287篇 |
2011年 | 323篇 |
2010年 | 199篇 |
2009年 | 174篇 |
2008年 | 269篇 |
2007年 | 300篇 |
2006年 | 278篇 |
2005年 | 250篇 |
2004年 | 294篇 |
2003年 | 252篇 |
2002年 | 241篇 |
2001年 | 197篇 |
2000年 | 193篇 |
1999年 | 173篇 |
1998年 | 66篇 |
1997年 | 78篇 |
1996年 | 61篇 |
1995年 | 68篇 |
1994年 | 58篇 |
1993年 | 44篇 |
1992年 | 129篇 |
1991年 | 114篇 |
1990年 | 111篇 |
1989年 | 113篇 |
1988年 | 102篇 |
1987年 | 110篇 |
1986年 | 88篇 |
1985年 | 92篇 |
1984年 | 66篇 |
1983年 | 45篇 |
1982年 | 53篇 |
1981年 | 38篇 |
1980年 | 25篇 |
1979年 | 48篇 |
1978年 | 25篇 |
1977年 | 26篇 |
1976年 | 18篇 |
1975年 | 21篇 |
1974年 | 24篇 |
1973年 | 32篇 |
排序方式: 共有6192条查询结果,搜索用时 15 毫秒
941.
942.
Inositol 2-dehydrogenase (EC 1.1.1.18) activity appears during growth of Bacillus subtilis (strain 60015) in nutrient sporulation medium. Its synthesis is induced by myo-inositol and repressed by D-glucose. The enzyme has an apparent molecular weight of 155,000 to 160,000 as determined by sucrose density gradient centrifugation, and it is comprised of four subunits, each having a molecular weight of 39,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The isoelectric point of the enzyme is 4.4 as determined by column isoelectric focusing. The enzyme shows the highest Vmax and lowest Km with myo-inositol as substrate but does not react with scyllo-inositol; it also reacts with the alpha anomer (but not the beta anomer) of D-glucose and with D-xylose. Apparently, the enzyme can remove only the single equatorial hydrogen of the cyclitol or pyranose ring. In contrast to the glucose dehydrogenase of spores, which reacts with D-glucose or 2-deoxy-D-glucose and with NAD or NADP, inositol dehydrogenase requires NAD and does not react with 2-deoxy-D-glucose. 相似文献
943.
Ayumu Niida Yoko Kanematsu-Yamaki Tomoko Asakawa Yoshimasa Ishimura Hisashi Fujita Kouta Matsumiya Naoki Nishizawa Yusuke Adachi Taisuke Mochida Kazue Tsuchimori Mariko Yoneyama-Hirozane Junichi Sakamoto Hideki Hirabayashi Hideo Fukui Shiro Takekawa Taiji Asami 《Bioorganic & medicinal chemistry》2018,26(3):566-572
Neuropeptide Y2 receptor (Y2R) agonism is an important anorectic signal and a target of antiobesity drug discovery. Recently, we synthesized a short-length Y2R agonist, PYY-1119 (4-imidazolecarbonyl-[d-Hyp24,Iva25,Pya(4)26,Cha27,36,γMeLeu28,Lys30,Aib31]PYY(23–36), 1) as an antiobesity drug candidate. Compound 1 induced marked body weight loss in diet-induced obese (DIO) mice; however, 1 also induced severe vomiting in dogs at a lower dose than the minimum effective dose administered to DIO mice. The rapid absorption of 1 after subcutaneous administration caused the severe vomiting. Polyethylene glycol (PEG)- and alkyl-modified derivatives of 1 were synthesized to develop Y2R agonists with improved pharmacokinetic profiles, i.e., lower maximum plasma concentration (Cmax) and longer time at maximum concentration (Tmax). Compounds 5 and 10, modified with 20?kDa PEG at the N-terminus and eicosanedioic acid at the Lys30 side chain of 1, respectively, showed high Y2R binding affinity and induced significant body weight reduction upon once-daily administration to DIO mice. Compounds 5 and 10, with their relatively low Cmax and long Tmax, partially attenuated emesis in dogs compared with 1. These results indicate that optimization of pharmacokinetic properties of Y2R agonists is an effective strategy to alleviate emesis induced by Y2R agonism. 相似文献
944.
Dequan Liu Yongliang Yan Yasunari Fujita Donghe Xu 《Molecular breeding : new strategies in plant improvement》2018,38(4):45
Soybean is highly sensitive to photoperiod. To improve the adaptability and productivity of soybean, it is essential to understand the molecular mechanisms regulating flowering time. To identify new flowering time QTLs, we evaluated a BC3F5 population consisting of 120 chromosome segment substitution lines (CSSLs) over 2 years under field conditions. CSSLs were derived from a cross between the cultivated soybean cultivar Jackson and the wild soybean accession JWS156-1, followed by continuous backcrossing using Jackson as the recurrent parent. Four QTLs (qFT07.1, qFT12.1, qFT12.2, and qFT19.1) were detected on three chromosomes. Of these, qFT12.1 showed the highest effect, accounting for 36.37–38.27% of the total phenotypic variation over 2 years. This QTL was further confirmed in the F7 recombinant inbred line population (n?=?94) derived from the same cross (Jackson × JWS156-1). Analysis of the qFT12.1 BC3F5 residual heterozygous line RHL509 validated the allele effect of qFT12.1 and revealed that the recessive allele of qFT12.1 resulted in delayed flowering. Evaluating the qFT12.1 near-isogenic lines (NILs) under different growth conditions showed that NILs with the wild soybean genotype always showed later flowering than those with the cultivated soybean genotype. qFT12.1 was delimited to a 2703-kb interval between the markers BARCSOYSSR_12_0220 and BARCSOYSSR_12_0368 on chromosome 12. qFT12.1 may be a new flowering time gene locus in soybean. 相似文献
945.
Miyuki Kusajima Shuhei Shima Moeka Fujita Kiwamu Minamisawa Fang-Sik Che Hiromoto Yamakawa 《Bioscience, biotechnology, and biochemistry》2018,82(9):1522-1526
A bacterial endophyte Azospirillum sp. B510 induces systemic disease resistance in the host without accompanying defense-related gene expression. To elucidate molecular mechanism of this induced systemic resistance (ISR), involvement of ethylene (ET) was examined using OsEIN2-knockdown mutant rice. Rice blast inoculation assay and gene expression analysis indicated that ET signaling is required for endophyte-mediated ISR in rice.
Abbreviations: ACC: 1-aminocyclopropane-1-carboxylic acid; EIN2: ethylene-insensitive protein 2; ET: ethylene; ISR: induced systemic resistance; JA: jasmonic acid; RNAi: RNA interference; SA: salicylic acid; SAR: systemic acquired resistance 相似文献
946.
Ubiquitin-activating enzyme (E1), which catalyzes the activation of ubiquitin in the initial step of the ubiquitination cascade, is a potential therapeutic target in multiple myeloma and breast cancer treatment. However, only a few E1 inhibitors have been reported to date. Moreover, there has been little medicinal chemistry research on the three-dimensional structure of E1. Therefore, in the present study, we attempted to identify novel E1 inhibitors using structure-based drug design. Following the rational design, synthesis, and in vitro biological evaluation of several such compounds, we identified a reversible E1 inhibitor (4b). Compound 4b increased p53 levels in MCF-7 breast cancer cells and inhibited their growth. These findings suggest that reversible E1 inhibitors are potential anticancer agents. 相似文献
947.
We introduce the principle of a new technique to isolate glycosphingolipids (GSLs) from phospholipids. Neutral and acidic GSLs in organic solvent bind to titanium dioxide under neutral pH and can be eluted with 5 mg/ml of 2,5-dihydroxybenzoic acid in methanol. This special property is applicable for eliminating phospholipids, including sphingomyelin, which cannot be eliminated by a typical mild alkaline treatment. By using this technique, we demonstrated the rapid separation of minor components of GSLs, namely sulfatide and gangliosides from rabbit serum and liver, respectively. The minor GSL components were effectively purified despite both sources containing tremendous amount of phospholipids and simple lipids such as cholesterol, cholesteryl esters and triglycerides. 相似文献
948.
ICAMs Are Not Obligatory for Functional Immune Synapses between Naive CD4 T Cells and Lymph Node DCs
949.
Nitric oxide-induced salt stress tolerance in plants: ROS metabolism,signaling, and molecular interactions 总被引:2,自引:0,他引:2
Mirza Hasanuzzaman Hirosuke Oku Kamrun Nahar M. H. M. Borhannuddin Bhuyan Jubayer Al Mahmud Frantisek Baluska Masayuki Fujita 《Plant biotechnology reports》2018,12(2):77-92
Nitric oxide (NO), a non-charged, small, gaseous free-radical, is a signaling molecule in all plant cells. Several studies have proposed multifarious physiological roles for NO, from seed germination to plant maturation and senescence. Nitric oxide is thought to act as an antioxidant, quenching ROS during oxidative stress and reducing lipid peroxidation. NO also mediates photosynthesis and stomatal conductance and regulates programmed cell death, thus providing tolerance to abiotic stress. In mitochondria, NO participates in the electron transport pathway. Nitric oxide synthase and nitrate reductase are the key enzymes involved in NO-biosynthesis in aerobic plants, but non-enzymatic pathways have been reported as well. Nitric oxide can interact with a broad range of molecules, leading to the modification of protein activity, GSH biosynthesis, S-nitrosylation, peroxynitrite formation, proline accumulation, etc., to sustain stress tolerance. In addition to these interactions, NO interacts with fatty acids to form nitro-fatty acids as signals for antioxidant defense. Polyamines and NO interact positively to increase polyamine content and activity. A large number of genes are reprogrammed by NO; among these genes, proline metabolism genes are upregulated. Exogenous NO application is also shown to be involved in salinity tolerance and/or resistance via growth promotion, reversing oxidative damage and maintaining ion homeostasis. This review highlights NO-mediated salinity-stress tolerance in plants, including NO biosynthesis, regulation, and signaling. Nitric oxide-mediated ROS metabolism, antioxidant defense, and gene expression and the interactions of NO with other bioactive molecules are also discussed. We conclude the review with a discussion of unsolved issues and suggestions for future research. 相似文献
950.
Hiroshi Hasegawa Ayumi Nozawa Rimana Islam Papry Teruya Maki Osamu Miki M. Azizur Rahman 《Journal of applied phycology》2018,30(4):2215-2225
Iron (Fe) is an important nutrient for phytoplankton. The low solubility of Fe in oxic waters can be a growth-limiting factor for phytoplankton. Synthetic aminopolycarboxylates (APCs) such as ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) are widely used as Fe complexing agents for microalgae culture. However, the presence of these non-ready biodegradable APCS in aquatic systems may have serious environmental consequences. In the present study, the effects of biodegradable chelating ligands (hydroxyiminodisuccinic acid (HIDS), methylglycinediacetic acid (MGDA), and iminodisuccinate (IDS)) on Fe uptake in and growth of three coastal microalgae (Heterosigma akashiwo, Prymnesium parvum, and Skeletonema marinoi-dohrnii complex) were investigated, and the results were compared with those of non-ready biodegradable APCs (EDTA, ethylenediamine tetra-methylene phosphonic acid (EDTMP), and DTPA). The biodegradable chelating ligands did not have significant growth inhibition effect on the phytoplankton. Although the growth of the algae (except S. marinoi-dohrnii complex) was not affected substantially by 1.5 and 7.5 μM of DTPA, growth inhibition occurred by 7.5 μM of EDTMP and 150 μM of EDTA, DTPA, and EDTMP. The effect of chelating ligands on microalgal growth was likely to be associated with the intracellular Fe uptake influenced by the chelating ligands. On average, intracellular Fe concentrations for biodegradable chelating ligands were substantially higher than those for non-ready biodegradable APCs. Except H. akashiwo, the ratio of intra/extracellular Fe concentrations was highest for MGDA followed by IDS and HIDS. The results indicate that biodegradable chelating ligands are more efficient than non-ready biodegradable APCs in intracellular Fe uptake and algal growth. 相似文献