全文获取类型
收费全文 | 224篇 |
免费 | 14篇 |
出版年
2019年 | 2篇 |
2018年 | 5篇 |
2017年 | 2篇 |
2016年 | 5篇 |
2015年 | 2篇 |
2014年 | 6篇 |
2013年 | 7篇 |
2012年 | 9篇 |
2011年 | 7篇 |
2010年 | 4篇 |
2009年 | 4篇 |
2008年 | 6篇 |
2007年 | 8篇 |
2006年 | 5篇 |
2005年 | 11篇 |
2004年 | 11篇 |
2003年 | 3篇 |
2002年 | 4篇 |
2001年 | 10篇 |
2000年 | 10篇 |
1999年 | 6篇 |
1998年 | 7篇 |
1997年 | 4篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1993年 | 2篇 |
1992年 | 8篇 |
1991年 | 4篇 |
1990年 | 7篇 |
1989年 | 4篇 |
1988年 | 11篇 |
1987年 | 5篇 |
1986年 | 5篇 |
1985年 | 3篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1982年 | 5篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 5篇 |
1973年 | 3篇 |
1972年 | 3篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1967年 | 2篇 |
排序方式: 共有238条查询结果,搜索用时 15 毫秒
51.
Katsuhiro Shiratake Yoshinori Kanayama Masayoshi Maeshima Shohei Yamaki 《Physiologia plantarum》1998,103(3):312-319
Protoplasts isolated from pear fruit at the end of the cell‐division stage, 30 days after flowering (DAF), had already formed a large central vacuole and the vacuole occupied most of the protoplast. The changes in protein composition and density of the tonoplast (vacuolar membrane) were investigated during fruit development. After a linear sucrose density gradient centrifugation, the distribution of tonoplasts at 30 and 48 DAF was broad and began to narrow with further fruit development. This suggests that the tonoplast of young fruit is heterogeneous and becomes homogeneous with fruit development. The apparent density of the tonoplast at 30 DAF was approximately 1.12 g ml−1 ; it decreased with fruit development and was finally 1.09 g ml−1 in mature fruit. The phospholipid amount on the basis of tonoplast protein was 0.80 mg mg−1 at 30 DAF. It increased with fruit development, and finally reached 7.49 mg mg−1 . This result indicates that the decrease in the density of the tonoplast was caused by the increase in the ratio of phospholipid to membrane protein. The protein composition of the tonoplast at each stage was quite different. The level of polypeptides of 94, 70, 61, 52, 48 and 41 kDa was low in young fruit and high in the middle or later stages of fruit development. In contrast, the level of a 76‐kDa polypeptide was high in young fruit and decreased with fruit development. Although their functions are still unclear, these tonoplast proteins may play important roles in fruit development. 相似文献
52.
K Kubota H Yamaki T Nishimura 《Biochemical and biophysical research communications》1973,52(2):489-495
In cell-free protein synthesis by the murine plasmacytoma X5563, which had become a nonproducing mutant, mixed systems with free polyribosomes and mirosomes incorporated 14C-amino-acid into protein 3–8 times greater than the sum of the incorporations in the individual system irrespective of S-100 concentrations. This enhancement was inhibited by lecithinase A and was markedly reduced at high KCl concentrations. Smooth endoplasmic membranes had more stimulatory activity than rough endoplasmic membranes. The results indicate that the membrane of the endoplasmic reticulum and free polyribosomes interact in the cell-free protein-synthesizing system, resulting in the enhancement of protein synthesis. 相似文献
53.
54.
Isolation of Vacuoles from Immature Apple Fruit Flesh and Compartmentation of Sugars, Organic Acids, Phenolic Compounds and Amino Acids 总被引:4,自引:0,他引:4
Vacuoles of immature apple fruit (Malus pumila Mill. var. domesticaSchneid.) were obtained by purification using Ficoll densitygradient centrifugation after lysis of the protoplasts by bothmild osmotic shock and the addition of EDTA and BSA. The recoverywas about 35% of the protoplasts. The isolated vacuoles hada mean diameter of about 100 µm. The distribution of sugars, organic acids, phenolic compoundsand amino acids in the vacuole, the cytoplasm and the free spacewas determined. Almost all of the fructose and glucose, themajor sugars of the tissue, were found in the vacuole. Sorbitolwas mainly located in the free space and the vacuole, and sucrosein the free space and the cytoplasm. More than 90% of the malicacid, the main organic acid, was located in the vacuole. Almostall of the phenolic compounds were also deposited in the vacuole. The volumes of the vacuole, the cytoplasm and the free spacein the whole tissue were calculated from the cell numbers ofthe whole tissue, the volume of the isolated protoplasts, andthe volume of the vacuoles present in the protoplast. The soluteconcentration in each compartment was estimated: vacuoles, 888mM; cytoplasm, 37 mM; free space, 57 mM. How these compartmentationsof solutes affected the translocation of sugars into the fruitand the cell expansion is discussed.
1This paper is contribution A-159 of the Fruit Tree ResearchStation. (Received July 7, 1983; Accepted November 14, 1983) 相似文献
55.
Cranial placodes are specialized ectodermal regions in the developing vertebrate head that give rise to both neural and non-neural cell types of the neuroendocrine system and the sense organs of the visual, olfactory and acoustic systems. The cranial placodes develop from a panplacodal region which is specifically marked by genes of the eyes absent/eya and two “six homeobox” family members (sine oculis/six1 and six4). It had been believed that cranial placodes are evolutionary novelties of vertebrates. However, data from non-vertebrate chordates suggest that placode-like structures evolved in the chordate ancestor already. Here, we identify a morphological structure in the embryonic head of the beetle Tribolium castaneum with placode-like features. It is marked by the orthologs of the panplacodal markers Tc-six4, Tc-eya and Tc-sine oculis/six1 (Tc-six1) and expresses several genes known to be involved in adenohypophyseal placode development in vertebrates. Moreover, it contributes to both epidermal and neural tissues. We identify Tc-six4 as a specific marker for this structure that we term the insect head placode. Finally, we reveal the regulatory gene network of the panplacodal genes Tc-six4, Tc-eya and Tc-six1 and identify them as head epidermis patterning genes. Our finding of a placode-like structure in an insect suggests that a placode precursor was already present in the last common ancestor of bilaterian animals. 相似文献
56.
Andrew KJ Boyce Ross T Prager Leigh E Wicki-Stordeur Leigh Anne Swayne 《Channels (Austin, Tex.)》2014,8(2):110-117
Pannexins (Panxs) are a multifaceted family of ion and metabolite channels that play key roles in a number of physiological and pathophysiological settings. These single membrane large-pore channels exhibit a variety of tissue, cell type, and subcellular distributions. The lifecycles of Panxs are complex, yet must be understood to accurately target these proteins for future therapeutic use. Here we review the basics of Panx function and localization, and then analyze the recent advances in knowledge regarding Panx trafficking. We examine several intrinsic features of Panxs including specific post-translational modifications, the divergent C-termini, and oligomerization, all of which contribute to Panx anterograde transport pathways. Further, we examine the potential influence of extrinsic factors, such as protein-protein interactions, on Panx trafficking. Finally, we highlight what is currently known with respect to Panx internalization and retrograde transport, and present new data illustrating Panx1 internalization following an activating stimulus. 相似文献
57.
Calmodulin purified from bovine brain markedly stimulated cyclic GMP-dependent protein kinase from pig lung in the presence of cyclic GMP. This stimulation by calmodulin did not require Ca2+ and was dose-dependent up to optimal amounts, but the extent of stimulation decreased at concentrations over the optimal condition. The concentrations of cyclic GMP and cyclic AMP producing half-maximal stimulation were 4.5 × 10?8 M and 5.0 × 10?6 M respectively, under optimal conditions. Calmodulin increased maximum velocity without altering the Km for ATP. These effects of calmodulin on cyclic GMP-dependent protein kinase were similar to those of the stimulatory modulator described by Kuo and Kuo (J. Biol. Chem. , 4283–4286, 1976). Ouf findings indicate that calmodulin regulates enzyme activity both Ca2+-dependently and independently. 相似文献
58.
Soo Lim Jeong Hongyu Zhang Shanni Yamaki Chenyu Yang David
D McKemy Michael
R Lieber Phuong Pham Myron
F Goodman 《Nucleic acids research》2022,50(20):11738
We describe a purified biochemical system to produce monoclonal antibodies (Abs) in vitro using activation-induced deoxycytidine deaminase (AID) and DNA polymerase η (Polη) to diversify immunoglobulin variable gene (IgV) libraries within a phage display format. AID and Polη function during B-cell affinity maturation by catalyzing somatic hypermutation (SHM) of immunoglobulin variable genes (IgV) to generate high-affinity Abs. The IgV mutational motif specificities observed in vivo are conserved in vitro. IgV mutations occurred in antibody complementary determining regions (CDRs) and less frequently in framework (FW) regions. A unique feature of our system is the use of AID and Polη to perform repetitive affinity maturation on libraries reconstructed from a preceding selection step. We have obtained scFv Abs against human glucagon-like peptide-1 receptor (GLP-1R), a target in the treatment of type 2 diabetes, and VHH nanobodies targeting Fatty Acid Amide Hydrolase (FAAH), involved in chronic pain, and artemin, a neurotropic factor that regulates cold pain. A round of in vitro affinity maturation typically resulted in a 2- to 4-fold enhancement in Ab-Ag binding, demonstrating the utility of the system. We tested one of the affinity matured nanobodies and found that it reduced injury-induced cold pain in a mouse model. 相似文献
59.
Toshihiro Hamajima Fumie Takahashi Koji Kato Koichiro Mukoyoshi Kousei Yoshihara Susumu Yamaki Yukihito Sugano Ayako Moritomo Kaoru Yamagami Koji Yokoo Hidehiko Fukahori 《Bioorganic & medicinal chemistry》2018,26(9):2410-2419
Phosphatidylinositol-3-kinase (PI3K)δ inhibition is one of the most attractive approaches to the treatment of autoimmune diseases and leukocyte malignancies. Through the exploration of pyrazolopyridine derivatives as potential PI3Kδ inhibitors, compound 12a was identified as a potent PI3Kδ inhibitor but suffered from poor oral exposure in mice. With a modified amide linkage group, compound 15a was developed as an orally available PI3Kδ inhibitor with reduced selectivity against other PI3Ks. To improve the trade-off between selectivity and PK profile, structure–activity relationship (SAR) studies of terminal substituents on the pyrolidine ring were conducted. As a result, we developed potent PI3Kδ inhibitors with good oral availability. In particular, the representative compound 15j showed excellent selectivity for PI3Kδ over other PI3Ks with good oral exposure in mice. 相似文献
60.
Toshihiro Hamajima Fumie Takahashi Koji Kato Yukihito Sugano Susumu Yamaki Ayako Moritomo Satoshi Kubo Koji Nakamura Kaoru Yamagami Nozomu Hamakawa Koji Yokoo Hidehiko Fukahori 《Bioorganic & medicinal chemistry》2018,26(14):3917-3924
Chemical optimization of pyrazolopyridine 1, focused on cellular potency, isoform selectivity and microsomal stability, led to the discovery of the potent, selective and orally available PI3Kδ inhibitor 5d. On the basis of its desirable potency, selectivity and pharmacokinetic profiles, 5d was tested in the trinitrophenylated aminoethylcarboxymethyl-Ficoll (TNP-Ficoll)-induced antibody production model, and showed higher antibody inhibition than a 4-fold oral dose of the starting compound 1. These excellent results suggest that 5d is a potential candidate for further studies in the treatment of autoimmune diseases and leukocyte malignancies. 相似文献