全文获取类型
收费全文 | 1383篇 |
免费 | 88篇 |
国内免费 | 1篇 |
出版年
2022年 | 7篇 |
2021年 | 18篇 |
2020年 | 5篇 |
2019年 | 17篇 |
2018年 | 14篇 |
2017年 | 23篇 |
2016年 | 31篇 |
2015年 | 37篇 |
2014年 | 57篇 |
2013年 | 98篇 |
2012年 | 78篇 |
2011年 | 77篇 |
2010年 | 35篇 |
2009年 | 58篇 |
2008年 | 74篇 |
2007年 | 69篇 |
2006年 | 55篇 |
2005年 | 74篇 |
2004年 | 77篇 |
2003年 | 54篇 |
2002年 | 69篇 |
2001年 | 28篇 |
2000年 | 42篇 |
1999年 | 37篇 |
1998年 | 18篇 |
1997年 | 17篇 |
1996年 | 22篇 |
1995年 | 14篇 |
1994年 | 7篇 |
1993年 | 13篇 |
1992年 | 24篇 |
1991年 | 14篇 |
1990年 | 18篇 |
1989年 | 20篇 |
1988年 | 27篇 |
1987年 | 27篇 |
1986年 | 16篇 |
1985年 | 12篇 |
1984年 | 8篇 |
1983年 | 13篇 |
1982年 | 13篇 |
1981年 | 4篇 |
1980年 | 7篇 |
1979年 | 6篇 |
1978年 | 3篇 |
1977年 | 7篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1974年 | 6篇 |
1973年 | 7篇 |
排序方式: 共有1472条查询结果,搜索用时 140 毫秒
991.
Matsumoto K Sakai H Ohta K Kameda H Sugawara F Abe M Sakaguchi K 《Chemistry and physics of lipids》2005,133(2):203-214
Physicochemical properties of 1,2-di-O-stearoyl-3-O-(6-deoxy-6-sulfo-alpha-D-glucopyranosyl)-sn-glycerol (alpha-SQDG-C(18:0)) and 1,2-di-O-stearoyl-3-O-(6-deoxy-6-sulfo-beta-D-glucopyranosyl)-sn-glycerol (beta-SQDG-C(18:0)) in monolayer and bilayer membranes were examined. Surface pressure measurements in monolayer membranes indicated the molecular area of beta-SQDG-C(18:0) to be slightly smaller than that of alpha-SQDG-C(18:0). In bilayer membranes, the phase transition temperature and the enthalpy of beta-SQDG-C(18:0) were higher than those of alpha-SQDG-C(18:0), while the trapping efficiency of beta-SQDG-C(18:0) vesicles was lower. The results suggested tighter packing with beta-SQDG-C(18:0) than alpha-SQDG-C(18:0), due to differences in the head group stereochemistry. High-performance liquid chromatography-electrospray ionization ion trap mass spectrometry (HPLC-ESI-MS) data and computational modeling studies provided supporting evidence for morphological differences. In both monolayer and bilayer membranes, the affinity of beta-SQDG-C(18:0) with cholesterol was greater than that of alpha-SQDG-C(18:0), again due to the differences in head group properties. Turbidity measurement and microscopic examination of alpha- and beta-SQDG-C(18:0)/cholesterol mixtures confirmed formation of large vesicles. The addition of cholesterol to SQDG-C(18:0) optimized membrane formation and stabilized its structure. 相似文献
992.
It is well known that human organic anion transporter 1 (hOAT1) transports many kinds of drugs, endogenous compounds, and toxins. However, little is known about the structure-affinity relationship. The aim of this study was to elucidate the structure-affinity relationship using a series of structurally related compounds that interact with hOAT1. Inhibitory effects of xanthine- and uric acid-related compounds on the transport of p-aminohippuric acid were examined using CHO-K1 cells stably expressing hOAT1. The order of potency for the inhibitory effects of xanthine-related compounds on PAH uptake was 1-methyl derivative>7-methyl derivative>3-methyl derivative falling dotsxanthine>1,3,7-trimethyl derivative (caffeine). The order of potency of the inhibition was 1,3,7-trimethyluric acid>1,3-dimethyluric acid>1,7-dimethyluric acid>1-methyluric acid>uric acid. A significant correlation between inhibitory potency and lipophilicity of the tested uric acid-related compounds was observed. The main determinant of the affinity of xanthine-related compounds is the position of the methyl group. On the other hand, lipophilicity is the main determinant of the affinity of uric acid-related compounds. 相似文献
993.
Hosono M Sugawara S Ogawa Y Kohno T Takayanagi M Nitta K 《Biochimica et biophysica acta》2005,1725(2):160-173
A novel C-type lectin (OLABL) was isolated from the eggs of shishamo smelt [Osmerus (Spirinchus) lanceolatus] by affinity chromatography on asialofetuin-Sepharose. OLABL had a molecular mass of 29 kDa on SDS-PAGE under nonreducing conditions and two subunits with masses of 15 kDa (OLABL-H) and 14 kDa (OLABL-L) under reducing conditions. Thus, OLABL is a heterodimeric protein. cDNA sequence analysis revealed that the H- and L-subunits of OLABL were composed of 137 and 136 amino acid residues, respectively, and showed almost identical (95%) sequences, with slight differences in the N-terminal and C-terminal regions. Since each subunit contained only the characteristic motif of C-type lectin-like domain (CTLD), EPN-E-WND, OLABL is a member of group VII of the CTLD-containing protein family. Although OLABL had an EPN sequence that is known as a mannose-specific motif found in the collectin family, OLABL agglutinated rabbit erythrocytes without the addition of Ca(2+) ion, and this activity was inhibited by l-rhamnose and d-galactose derivatives, but not by d-mannose and d-glucose. These results indicate that OLABL has similar characteristics to AJL-2, a calcium-independent lactose specific lectin isolated from Japanese eel skin mucus. Recombinant OLABLs (rHisOLABLs), His-tagged homodimers of the H- and L-subunits, were refolded from inclusion bodies expressed by Escherichia coli. rHisOLABL-L was recovered as a soluble form, but rHisOLABL-H was hardly dissolved in a renaturing buffer. The specific activities of rHisOLABL-L, rHisOLABL-H, and native OLABL were 500, 36, and 20, respectively. These findings suggest that the combination of subunits may affect the solubility and activity of these dimeric form lectins. 相似文献
994.
Matsui Y Otomo K Ishida S Yanagihara K Kawanobe Y Kida S Taruoka E Sugawara I 《Microbiology and immunology》2004,48(7):489-495
The antimycobacterial activity of "Hikari-Gintech" powder, which has photocatalytic activity, was examined in vitro. Both powder dissolved in liquid and Hikari-Gintech-coated cloths showed strong antimycobacterial activity against Mycobacterium tuberculosis H37Rv, M. bovis BCG Pasteur, multi-drug-resistant M. tuberculosis (a clinical isolate) and M. avium. Hikari-Gintech powder appeared to affect mycobacterial cell wall metabolism rather than mycobacterial DNA because no damage to mycobacterial DNA was detected after spraying with Hikari-Gintech solution. 相似文献
995.
Takahashi H Rai M Kitagawa T Morita S Masumura T Tanaka K 《Bioscience, biotechnology, and biochemistry》2004,68(8):1728-1736
Tonoplast intrinsic proteins (TIPs) belong to an aquaporin family of proteins that function as water-transport channels. In this study, we isolated and characterized three novel rice cDNAs for OsTIP1, OsTIP2, and OsTIP3 that are homologous to rice gamma-TIP cDNA. Northern blot hybridization analyses revealed that rice gamma-TIP was expressed in all plant organs. OsTIP1 was expressed in mature seed embryos and during early seed germination. OsTIP2 was expressed exclusively in roots. OsTIP3 was specifically expressed in seeds. These results suggest that the OsTIP1, OsTIP2, and OsTIP3 genes encode discrete, functionally specialized TIPs. Immunocytochemical analysis in rice endosperm cells revealed that rice gamma-TIP was localized only on the protein body type II (PB-II) membranes, whereas OsTIP3 was localized on the PB-II and the aleurone grain membranes. Although both the PB-II and the aleurone grain are derived from vacuoles, these results suggest that they may be derived from different types of vacuoles. 相似文献
996.
Repairing a double-strand chromosome break by homologous recombination: revisiting Robin Holliday's model 总被引:4,自引:0,他引:4
Haber JE Ira G Malkova A Sugawara N 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2004,359(1441):79-86
Since the pioneering model for homologous recombination proposed by Robin Holliday in 1964, there has been great progress in understanding how recombination occurs at a molecular level. In the budding yeast Saccharomyces cerevisiae, one can follow recombination by physically monitoring DNA after the synchronous induction of a double-strand break (DSB) in both wild-type and mutant cells. A particularly well-studied system has been the switching of yeast mating-type (MAT) genes, where a DSB can be induced synchronously by expression of the site-specific HO endonuclease. Similar studies can be performed in meiotic cells, where DSBs are created by the Spo11 nuclease. There appear to be at least two competing mechanisms of homologous recombination: a synthesis-dependent strand annealing pathway leading to noncrossovers and a two-end strand invasion mechanism leading to formation and resolution of Holliday junctions (HJs), leading to crossovers. The establishment of a modified replication fork during DSB repair links gene conversion to another important repair process, break-induced replication. Despite recent revelations, almost 40 years after Holliday's model was published, the essential ideas he proposed of strand invasion and heteroduplex DNA formation, the formation and resolution of HJs, and mismatch repair, remain the basis of our thinking. 相似文献
997.
Yonemura H Imamura T Soejima K Nakahara Y Morikawa W Ushio Y Kamachi Y Nakatake H Sugawara K Nakagaki T Nozaki C 《Journal of biochemistry》2004,135(5):577-582
We have established a large-scale manufacturing system to produce recombinant human alpha-thrombin. In this system, a high yield of alpha-thrombin is prepared from prethrombin-2 activated by recombinant ecarin. We produced human prethrombin-2 using mouse myeloma cells and an expression plasmid carrying the chicken beta-actin promoter and mutant dihydrofolate reductase gene for gene amplification. To increase prethrombin-2 expression further, we performed fed-batch cultivation with the addition of vegetable peptone in 50 liters of suspension culture. After five feedings of vegetable peptone, the expression level of the recombinant prethrombin-2 reached 200 micro g/ml. Subsequently, the recombinant prethrombin-2 could be activated to alpha-thrombin by recombinant ecarin expressed in a similar manner. Finally, recombinant alpha-thrombin was purified to homogeneity by affinity chromatography using a benzamidine-Sepharose gel. The yield from prethrombin-2 in culture medium was approximately 70%. The activity of the purified recombinant alpha-thrombin, including hydrolysis of a chromogenic substrate, release of fibrinopeptide A, and activation of protein C, was indistinguishable from that of plasma-derived alpha-thrombin. Our system is suitable for the large-scale production of recombinant alpha-thrombin, which can be used in place of clinically available alpha-thrombin derived from human or bovine plasma. 相似文献
998.
Nishimura H Nishimura M Oda R Yamanaka K Matsubara T Ozaki Y Sekiya K Hamada T Kato Y 《Experimental cell research》2004,295(1):119-127
Transplantation of bone marrow mesenchymal stem cells (MSC), chondrocytes, osteoblasts, or muscle cells promotes regeneration. However, these cells adhere poorly to some scaffolds--depending upon the scaffold material--and are often damaged by proteases or mechanical stimuli at site of transplantation. We found, however, that MSC, chondrocytes, and osteoblasts--along with some other cells--that were exposed to phaseolus vulgaris erythroagglutinin (PHA-E) or concanavalin A (ConA) increased their adhesion capacity on plastic tissue culture dishes and on plates of hydroxyapatite, titanium and poly-DL-lactic-co-glycolic acid (PLGA), and that these cells, moreover, built up resistance to proteases and/or mechanical stimuli. Thus, lectins may have great potential in tissue engineering and cell therapy. 相似文献
999.
Cloning and functional characterization of a new subtype of the amino acid transport system N 总被引:4,自引:0,他引:4
Nakanishi Takeo; Kekuda Ramesh; Fei You-Jun; Hatanaka Takahiro; Sugawara Mitsuru; Martindale Robert G.; Leibach Frederick H.; Prasad Puttur D.; Ganapathy Vadivel 《American journal of physiology. Cell physiology》2001,281(6):C1757
We have cloned a new subtype of theamino acid transport system N2 (SN2 or second subtype of system N) fromrat brain. Rat SN2 consists of 471 amino acids and belongs to therecently identified glutamine transporter gene family that consists ofsystem N and system A. Rat SN2 exhibits 63% identity with rat SN1. Italso shows considerable sequence identity (50-56%) with themembers of the amino acid transporter A subfamily. In the rat, SN2 mRNA is most abundant in the liver but is detectable in the brain, lung,stomach, kidney, testis, and spleen. When expressed in Xenopus laevis oocytes and in mammalian cells, rat SN2 mediatesNa+-dependent transport of several neutral amino acids,including glycine, asparagine, alanine, serine, glutamine, andhistidine. The transport process is electrogenic, Li+tolerant, and pH sensitive. The transport mechanism involves the influxof Na+ and amino acids coupled to the efflux ofH+, resulting in intracellular alkalization. Proline,-(methylamino)isobutyric acid, and anionic and cationic amino acidsare not recognized by rat SN2. 相似文献
1000.
Sugawara S Nemoto E Tada H Miyake K Imamura T Takada H 《Journal of immunology (Baltimore, Md. : 1950)》2000,165(1):411-418
Cysteine proteinases (gingipains) elaborated from Porphyromonas gingivalis exhibit enzymatic activities against a broad range of host proteins and are considered key virulence factors in the onset and development of adult periodontitis and host defense evasion. In this study, we examined the ability of arginine-specific gingipains (high molecular mass Arg-specific gingipain (HRGP) and Arg-specific gingipain 2) and lysine-specific gingipain (KGP) to cleave monocyte CD14, the main receptor for bacterial cell surface components such as LPS. Binding of anti-CD14 mAb MY4 to human monocytes was almost completely abolished by 0.3 microM HRGP and KGP treatments for 15 min, and 1 microM RGP2 for 30 min. In contrast, the expressions of Toll-like receptor 4, and CD18, CD54, CD59, and HLA-A, -B, -C on monocytes were slightly increased and decreased, respectively, by 0. 3 microM HRGP and KGP. This down-regulation resulted from direct proteolysis, because 1) gingipains eliminated MY4 binding even to fixed monocytes, and 2) CD14 fragments were detected in the extracellular medium by immunoblot analysis. Human rCD14 was degraded by all three gingipains, which confirmed that CD14 was a substrate for gingipains. TNF-alpha production by monocytes after HRGP and KGP treatments was decreased at 1 ng/ml, but not at 20 microg/ml LPS, indicating that gingipains inhibited a CD14-dependent cell activation. These results suggest that gingipains preferentially cleave monocyte CD14, resulting in attenuation of the cellular recognition of bacteria, and as a consequence sustain chronic inflammation. 相似文献