全文获取类型
收费全文 | 9331篇 |
免费 | 367篇 |
国内免费 | 61篇 |
专业分类
化学 | 6390篇 |
晶体学 | 93篇 |
力学 | 279篇 |
数学 | 808篇 |
物理学 | 2189篇 |
出版年
2023年 | 54篇 |
2022年 | 190篇 |
2021年 | 226篇 |
2020年 | 179篇 |
2019年 | 172篇 |
2018年 | 172篇 |
2017年 | 144篇 |
2016年 | 296篇 |
2015年 | 269篇 |
2014年 | 354篇 |
2013年 | 596篇 |
2012年 | 742篇 |
2011年 | 823篇 |
2010年 | 469篇 |
2009年 | 385篇 |
2008年 | 616篇 |
2007年 | 580篇 |
2006年 | 512篇 |
2005年 | 473篇 |
2004年 | 408篇 |
2003年 | 325篇 |
2002年 | 326篇 |
2001年 | 216篇 |
2000年 | 177篇 |
1999年 | 129篇 |
1998年 | 69篇 |
1997年 | 79篇 |
1996年 | 95篇 |
1995年 | 80篇 |
1994年 | 75篇 |
1993年 | 57篇 |
1992年 | 60篇 |
1991年 | 47篇 |
1990年 | 51篇 |
1989年 | 34篇 |
1988年 | 26篇 |
1987年 | 12篇 |
1986年 | 10篇 |
1985年 | 26篇 |
1984年 | 18篇 |
1983年 | 17篇 |
1982年 | 18篇 |
1981年 | 16篇 |
1980年 | 12篇 |
1979年 | 13篇 |
1978年 | 16篇 |
1977年 | 10篇 |
1976年 | 13篇 |
1975年 | 10篇 |
1972年 | 9篇 |
排序方式: 共有9759条查询结果,搜索用时 15 毫秒
61.
Park JB 《Experimental & molecular medicine》2003,35(5):325-335
Phagocytosis by inflammatory cells is an essential step and a part of innate immunity for protection against foreign pathogens, microorganism or dead cells. Phagocytosis, endocytotic events sequel to binding particle ligands to the specific receptors on phagocyte cell surface such as Fcgamma recptor (FcgammaR), complement receptor (CR), beta-glucan receptor, and phosphatidylserine (PS) receptor, require actin assembly, pseudopod extension and phagosome closure. Rho GTPases (RhoA, Cdc42, and Rac1) are critically involved in these processes. Abrupt superoxide formation, called as oxidative burst, occurs through NADPH oxidase complex in leukocytes following phagocytosis. NADPH oxidase complex is composed of membrane proteins, p22PHOX and gp91PHOX, and cytosolic proteins, p40PHOX, p47PHOX and p67PHOX. The cytosolic subunits and Rac-GTP are translocated to the membrane, forming complete NADPH oxidase complex with membrane part subunits. Binding of imunoglobulin G (IgG)- and complement-opsonized particles to FcgammaR and CR of leukocytes induces apoptosis of the cells, which may be due to oxidative burst and accompanying cytochrome c release and casapase-3 activation. 相似文献
62.
Heo YS Ryu JM Park SM Park JH Lee HC Hwang KY Kim J 《Experimental & molecular medicine》2002,34(3):211-223
Protein-tyrosine phosphatases (PTPs) constitute a family of receptor-like, and cytoplasmic enzymes, which catalyze the dephosphorylation of phosphotyrosine residues in a variety of receptors and signaling molecules. Together with protein tyrosine kinases (PTKs), PTPs are critically involved in regulating many cellular signaling processes. In this study, diverse compounds were screened for PTP inhibition and selectively screened for inhibitors with the end product inhibition properties. Among phosphate analogues and their derivatives for PTP inhibition, Keggin compounds phosphomolybdate (PM) and phosphotungstate (PT) strongly inhibited both PTP-1B and SHP-1, with K(i) values of 0.06-1.2 micromM in the presence of EDTA. Unlike the vanadium compounds, inhibition potencies of PM and PT were not significantly affected by EDTA. PM and PT were potent, competitive inhibitors for PTPs, but relatively poor inhibitors of Ser/Thr phosphatase. Interestingly, PM and PT did not inhibit alkaline phosphatase at all. The crystal structure of PTP-1B in complex with PM, at 2.0 A resolution, reveals that MoO(3), derived from PM by hydrolysis, binds at the active site. The molybdenium atom of the inhibitor is coordinated with six ligands: three oxo-ligands, two apical water molecules and a S atom of the catalytic cysteine residue. In support of the crystallographic finding, we observed that molybdenium oxides (MoO(3), MoO(2), and MoO(2)Cl(2)) inhibited PTP-1B with IC(50) in the range 5-15 micromM. 相似文献
63.
Jaehun Park Doug S. English Yvonne Wannemuehler Susan Carpenter Jacob W. Petrich 《Photochemistry and photobiology》1998,68(4):593-597
The light-induced antiviral activity of hypericin and hypocrellin in the presence and absence of oxygen was examined under experimental conditions where the effect of oxygen depletion could be quantified. There was a significant reduction of light-induced antiviral activity of hypericin and hypocrellin under hypoxic conditions. Interestingly, antiviral activity of hypocrellin was not observed at low oxygen levels at which hypericin retained measurable virucidal activity. This suggests that additional pathways, such as the generation of protons from excited states of hypericin, may enhance the biological activity of activated oxygen species. 相似文献
64.
Min Gyu Jeong Kai Zhou Soyeon Park HyeongJeon An Yonghoon Kwon Yeonho Chang Do-Hyeon Kim Sung Ho Ryu 《Experimental & molecular medicine》2021,53(2):291
Various repertoires of membrane protein interactions determine cellular responses to diverse environments around cells dynamically in space and time. Current assays, however, have limitations in unraveling these interactions in the physiological states in a living cell due to the lack of capability to probe the transient nature of these interactions on the crowded membrane. Here, we present a simple and robust assay that enables the investigation of transient protein interactions in living cells by using the single-molecule diffusional mobility shift assay (smDIMSA). Utilizing smDIMSA, we uncovered the interaction profile of EGFR with various membrane proteins and demonstrated the promiscuity of these interactions depending on the cancer cell line. The transient interaction profile obtained by smDIMSA will provide critical information to comprehend the crosstalk among various receptors on the plasma membrane.Subject terms: Fluorescence imaging, Super-resolution microscopy, Single-molecule biophysics 相似文献
65.
All four stereoisomers of 2-alkyl-3,4-iminobutanoic acid, a novel class of beta-amino acids bearing a chemically versatile aziridine ring, were synthesized starting with aspartic acid. The synthetic strategy involves the introduction of an alkyl group at the beta-position of fully protected optically active aspartic acid followed by the construction of an aziridine ring making use of the alpha-carboxylate and alpha-amino groups. The alpha-carboxylate was reduced to the corresponding alcohol, which was then subjected to cyclization to form an aziridine ring with the N-protected amino group. Removal of the protection groups yielded the target compounds. 相似文献
66.
Photoactivation of pheophorbide a induces a mitochondrial-mediated apoptosis in Jurkat leukaemia cells 总被引:5,自引:0,他引:5
Lee WY Lim DS Ko SH Park YJ Ryu KS Ahn MY Kim YR Lee DW Cho CW 《Journal of photochemistry and photobiology. B, Biology》2004,75(3):119-126
The mechanism of cell death by pheophorbide a (Pba) which has been established to be a potential photosensitizer was examined in experimental photodynamic therapy (PDT) on Jurkat cells, a human lymphoid tumor cell line. In 30-60 min after irradiation, Pba treated cells exhibited apoptotic features including membrane blebbing and DNA fragmentation. Pba/PDT caused a rapid release of cytochrome c from mitochondria into the cytosol. Sequentially, activation of caspase-3 and the cleavage of poly ADP-ribose polymerase (PARP) were followed. Meanwhile, no evidence of activation of caspase-8 was indicated in the cells. In experiments with caspase inhibitors, it was found that caspase-3 alone was sufficient initiator for the Pba-induced apoptosis of the cells. Pba specific emission spectra were confirmed in the mitochondrial fraction and the light irradiation caused a rapid change in its membrane potential. Thus, mitochondria were entailed as the crucial targets for Pba as well as a responsible component for the cytochrome c release to initiate apoptotic pathways. Taken together, it was concluded that the mode of Jurkat cell death by Pba/PDT is an apoptosis, which is initiated by mitochondrial cytochrome c release and caspase-3-pathways. 相似文献
67.
Uranium(VI) complexed with aluminon (3-[bis(3-carboxy-4-hydroxy-phenyl)methylene]-6-oxo-1,4-cyclohexadiene-1-carboxylic acid triammonium salt) was determined by adsorptive cathodic stripping voltammetry (ACSV) using a hanging mercury drop electrode. Trace uranium(VI) and zinc(II) can be simultaneously determined in a single scan in the presence of aluminon and urea. Optimal conditions were found to be: accumulation time; 180–200 s, accumulation potential; 50 mV versus Ag/AgCl, scan rate; 40 mV s−1, supporting electrolyte; 0.1 M sodium acetate buffer at pH 6.5–7.0, and concentration of aluminon; 1×10−6 M. The linear range of uranium(VI) and zinc(II) were observed over the concentration range 2–33 and 30–120 ng ml−1, respectively. The detection limit (S/N=3) are 0.2 ng ml−1 (uranium) and 30 ng ml−1 (zinc). A good reproducibility shows RSDs of 2.5–4.0% (n=10). The procedure offers high selectivity, with the presence of urea masking some metal ions. 相似文献
68.
Hong KM Choi YB Hong JH Chang HS Rhee KI Park H Paik MK 《Experimental & molecular medicine》1999,31(1):30-35
C-Terminal carboxyl methylation of a human placental 23 kDa protein catalyzed by membrane-associated methyltransferase has been investigated. The 23 kDa protein substrate methylated was partially purified by DEAE-Sephacel, hydroxyapatite and Sephadex G-100 gel filtration chromatographies. The substrate protein was eluted on Sephadex G-100 gel filtration chromatography as a protein of about 29 kDa. In the absence of Mg2+, the methylation was stimulated by guanine nucleotides (GTP, GDP and GTPgammaS), but in the presence of Mg2+, only GTPgammaS stimulated the methylation which was similar to the effect on the G25K/rhoGDI complex. AFC, an inhibitor of C-terminal carboxyl methylation, inhibited the methylation of human placental 23 kDa protein. These results suggests that the substrate is a small G protein different from the G25K and is methylated on C-terminal isoprenylated cysteine residue. This was also confirmed by vapor phase analysis. The methylated substrate protein was redistributed to membrane after in vitro methylation, suggesting that the methylation of this protein is important for the redistribution of the 23 kDa small G protein for its putative role in intracellular signaling. 相似文献
69.
The metabolites of trimeprazine were identified in urine of rats by gas chromatography-mass spectrometry. After the oral administration of trimeprazine, the urinary metabolites were extracted with diethyl ether before or after hydrolysis with beta-glucuronidase. The identified metabolites were N-demethyltrimeprazine,3-hydroxytrimeprazine,N-demethyl-3-++ +hydroxytrimeprazine and trimeprazine sulphoxide. 相似文献
70.
Procedures were developed for reducing the reaction time and improving the yield of reductive alkylation in solid phase pseudopeptide synthesis by utilizing microwave irradiation. We chose dipeptides containing the reduced amide bond ψ[CH2NH] as a model system and optimized the microwave assisted reductive alkylation reaction in solid phase pseudopeptide synthesis using Fmoc chemistry. Under the optimized condition, the reductive alkylation reaction used for incorporating the reduced amide bond into the dipeptides was completed in only 8.5 min, whereas the normal reductive alkylation reaction required a total of 300 min. The purity and yield of the various dipeptides containing the reduced amide bond synthesized in this way are better than those achieved using the reductive alkylation method without microwave irradiation. We chose α helical peptides, which are known as a difficult sequence to synthesize, and incorporated the reduced amide bond by the microwave-assisted reductive alkylation reaction. We successfully synthesized pseudopeptides containing the reduced amide bond as a major product by using the novel microwave-assisted method, whereas the same products were obtained as a minor product when using the reductive alkylation method without microwave irradiation. 相似文献