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951.
A general method for preparation of N‐Boc‐protected or N‐Fmoc‐protected α,β‐didehydropeptide building blocks and their use in the solid‐phase peptide synthesis
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N‐(tert‐butyloxycarbonyl) or N‐(9‐fluorenylmethoxycarbonyl) dipeptides with C‐terminal (Z)‐α,β‐didehydrophenylalanine (?ZPhe), (Z)‐α,β‐didehydrotyrosine (?ZTyr), (Z)‐α,β‐didehydrotryptophan (?ZTrp), (Z)‐α,β‐didehydromethionine (?ZMet), (Z)‐α,β‐didehydroleucine (?ZLeu), and (Z/E)‐α,β‐didehydroisoleucine (?Z/EIle) were synthesised from their saturated analogues via oxidation of intermediate 2,5‐disubstituted‐oxazol‐5‐(4H)‐ones (also known as azlactones) with pyridinium tribromide followed by opening of the produced unsaturated oxazol‐5‐(4H)‐one derivatives in organic‐aqueous solution with a catalytic amount of trifluoroacetic acid or by a basic hydrolysis. In all cases, a very strong preference for Z isomers of α,β‐didehydro‐α‐amino acid residues was observed except of the ΔIle, which was obtained as the equimolar mixture of Z and E isomers. Reasons for the (Z)‐stereoselectivity and the increased stability of the aromatic α,β‐didehydro‐α‐amino acid residue oxazol‐5‐(4H)‐ones over the corresponding aliphatic ones are also discussed. It is the first use of such a procedure to synthesise peptides with the C‐terminal unsaturated residues and a peptide with 2 consecutive ΔPhe residues. This approach is very effective especially in the synthesis of peptides with aliphatic α,β‐didehydro‐α‐amino acid residues that are difficult to obtain by other methods. It allowed the first synthesis of the ?Met residue. It is also more cost‐effective and less laborious than other synthesis protocols. The dipeptide building blocks obtained were used in the solid‐phase synthesis of model peptides on a polystyrene‐based solid support. Peptides containing aromatic α,β‐didehydro‐α‐amino acid residues were obtained with PyBOP or TBTU as a coupling agent with good yields and purities. In the case of aliphatic α,β‐didehydro‐α‐amino acid residues, a good efficiency was achieved only with DPPA as a coupling agent. 相似文献
952.
Izabela Sadowska-Bartosz Ireneusz Stefaniuk Bogumił Cieniek Grzegorz Bartosz 《Free radical research》2018,52(3):335-338
AbstractTEMPO-phosphate has been introduced as a phosphate analogue to study phosphate transport in erythrocytes. The nitroxide is reduced intracellularly upon entering the cells, the membrane transport being the rate-limiting step of the loss of ESR signal. The use of TEMPO-phosphate is convenient and avoids the hazard of radioactivity. We studied the inhibition of TEMPO-phosphate transport to human erythrocytes by various compounds. DIDS and SITS, inhibitors of Band 3, inhibited the TEMPO-phosphate transport. 1-cyano-4-hydroxycinnamic acid, inhibitor of monocarboxylate transporters, did not affect the permeation of TEMPO-phosphate. The transport of TEMPO-phosphate was inhibited by various polyphenols, especially curcumin, naringin, quercetin, luteolin and kaempferol. Interestingly, 3-bromopyruvic acid, an alkylating agent and potential anticancer agent, induced an apparent enhancement of TEMPO-phosphate transport into erythrocytes. 相似文献
953.
Nosema maddoxi sp. nov. (Microsporidia,Nosematidae), a Widespread Pathogen of the Green Stink Bug Chinavia hilaris (Say) and the Brown Marmorated Stink Bug Halyomorpha halys (Stål)
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Ann E. Hajek Leellen F. Solter Joseph V. Maddox Wei‐Fone Huang Alden S. Estep Grzegorz Krawczyk Donald C. Weber Kim A. Hoelmer Neil D. Sanscrainte James J. Becnel 《The Journal of eukaryotic microbiology》2018,65(3):315-330
We describe a unique microsporidian species that infects the green stink bug, Chinavia hilaris; the brown marmorated stink bug, Halyomorpha halys; the brown stink bug, Euschistus servus; and the dusky stink bug, Euschistus tristigmus. All life stages are unikaryotic, but analysis of the consensus small subunit region of the ribosomal gene places this microsporidium in the genus Nosema, which historically has been characterized by diplokaryotic life stages. It is also characterized by having the reversed arrangement of the ribosomal gene (LSU –ITS‐ SSU) found in species within the “true Nosema” clade. This microsporidium is apparently Holarctic in distribution. It is present in H. halys both where it is native in Asia and where it is invasive in North America, as well as in samples of North American native C. hilaris collected prior to the introduction of H. halys from Asia. Prevalence in H. halys from mid‐Atlantic, North America in 2015–2016 ranged from 0.0% to 28.3%, while prevalence in C. hilaris collected in Illinois in 1970–1972 ranged from 14.3% to 58.8%. Oral infectivity and pathogenicity were confirmed in H. halys and C. hilaris. Morphological, ultrastructural, and ecological features of the microsporidium, together with a molecular phylogeny, establish a new species named Nosema maddoxi sp. nov. 相似文献
954.
955.
956.
Feasibility of pathways for transfer of acyl groups from mitochondria to the cytosol to form short chain acyl-CoAs in the pancreatic beta cell 总被引:2,自引:0,他引:2
MacDonald MJ Smith AD Hasan NM Sabat G Fahien LA 《The Journal of biological chemistry》2007,282(42):30596-30606
The mitochondria of pancreatic beta cells are believed to convert insulin secretagogues into products that are translocated to the cytosol where they participate in insulin secretion. We studied the hypothesis that short chain acyl-CoA (SC-CoAs) might be some of these products by discerning the pathways of SC-CoA formation in beta cells. Insulin secretagogues acutely stimulated 1.5-5-fold increases in acetoacetyl-CoA, succinyl-CoA, malonyl-CoA, hydroxymethylglutaryl-CoA (HMG-CoA), and acetyl-CoA in INS-1 832/13 cells as judged from liquid chromatography-tandem mass spectrometry measurements. Studies of 12 relevant enzymes in rat and human pancreatic islets and INS-1 832/13 cells showed the feasibility of at least two redundant pathways, one involving acetoacetate and the other citrate, for the synthesis SC-CoAs from secretagogue carbon in mitochondria and the transfer of their acyl groups to the cytosol where the acyl groups are converted to SC-CoAs. Knockdown of two key cytosolic enzymes in INS-1 832/13 cells with short hairpin RNA supported the proposed scheme. Lowering ATP citrate lyase 88% did not inhibit glucose-induced insulin release indicating citrate is not the only carrier of acyl groups to the cytosol. However, lowering acetoacetyl-CoA synthetase 80% partially inhibited glucose-induced insulin release indicating formation of SC-CoAs from acetoacetate in the cytosol is important for insulin secretion. The results indicate beta cells possess enzyme pathways that can incorporate carbon from glucose into acetyl-CoA, acetoacetyl-CoA, and succinyl-CoA and carbon from leucine into these three SC-CoAs plus HMG-CoA in their mitochondria and enzymes that can form acetyl-CoA, acetoacetyl-CoA, malonyl-CoA, and HMG-CoA in their cytosol. 相似文献
957.
Exposing pups of the rodent species Octodon degus to periodic separation stress during the first three postnatal weeks leads to behavioral alterations, which include reduced attention towards an emotional stimulus and motoric hyperactivity. These behavioral changes, which are reminiscent of symptoms of attention deficit hyperactivity disorder (ADHD), are paralleled by synaptic changes in the dorsal anterior cingulate cortex (ACd), a limbic cortex region, which plays a key role in the modulation of attentional and executive functions. ADHD is typically treated with methylphenidate (MP), a drug acting on the dopaminergic system. However, the effect of chronic MP-treatment on neuronal and synaptic maturation in the developing brain is unknown. Applying the Golgi-Cox stainining technique, we tested in which way chronic MP-treatment interferes with dendritic and synaptic development in the ACd and whether this treatment can restore the stress-induced changes of neuronal connectivity. We found that chronic treatment with 1 mg/kg MP recovers stress-induced changes of spine densities in the ACd. Furthermore, MP-treatment resulted in increased dendritic length and complexity in both, stressed as well as unstressed control animals. These results indicate that synaptic reorganization as well as dendritic growth in the prefrontal cortex continue into prepuberty and are modulated by MP-treatment. 相似文献
958.
959.
TRPM8, a member of the transient receptor potential (TRP) channel superfamily, is expressed in thermosensitive neurons, in which it functions as a cold and menthol sensor. TRPM8 and most other temperature-sensitive TRP channels (thermoTRPs) are voltage gated; temperature and ligands regulate channel opening by shifting the voltage dependence of activation. The mechanisms and structures underlying gating of thermoTRPs are currently poorly understood. Here we show that charge-neutralizing mutations in transmembrane segment 4 (S4) and the S4-S5 linker of human TRPM8 reduce the channel's gating charge, which indicates that this region is part of the voltage sensor. Mutagenesis-induced changes in voltage sensitivity translated into altered thermal sensitivity, thereby establishing the strict coupling between voltage and temperature sensing. Specific mutations in this region also affected menthol affinity, which indicates a direct interaction between menthol and the TRPM8 voltage sensor. Based on these findings, we present a Monod-Wyman-Changeux-type model explaining the combined effects of voltage, temperature and menthol on TRPM8 gating. 相似文献
960.
Grzegorz Konert Gabor Steinbach Myriam Canonico Radek Kaa 《Physiologia plantarum》2019,166(1):264-277
A proper spatial distribution of photosynthetic pigment‐protein complexes – PPCs (photosystems, light‐harvesting antennas) is crucial for photosynthesis. In plants, photosystems I and II (PSI and PSII) are heterogeneously distributed between granal and stromal thylakoids. Here we have described similar heterogeneity in the PSI, PSII and phycobilisomes (PBSs) distribution in cyanobacteria thylakoids into microdomains by applying a new image processing method suitable for the Synechocystis sp. PCC6803 strain with yellow fluorescent protein‐tagged PSI. The new image processing method is able to analyze the fluorescence ratios of PPCs on a single‐cell level, pixel per pixel. Each cell pixel is plotted in CIE1931 color space by forming a pixel‐color distribution of the cell. The most common position in CIE1931 is then defined as protein arrangement (PA) factor with xy coordinates. The PA‐factor represents the most abundant fluorescence ratio of PSI/PSII/PBS, the ‘mode color’ of studied cell. We proved that a shift of the PA‐factor from the center of the cell‐pixel distribution (the ‘median’ cell color) is an indicator of the presence of special subcellular microdomain(s) with a unique PSI/PSII/PBS fluorescence ratio in comparison to other parts of the cell. Furthermore, during a 6‐h high‐light (HL) treatment, ‘median’ and ‘mode’ color (PA‐factor) of the cell changed similarly on the population level, indicating that such microdomains with unique PSI/PSII/PBS fluorescence were not formed during HL (i.e. fluorescence changed equally in the whole cell). However, the PA‐factor was very sensitive in characterizing the fluorescence ratios of PSI/PSII/PBS in cyanobacterial cells during HL by depicting a 4‐phase acclimation to HL, and their physiological interpretation has been discussed. 相似文献