全文获取类型
收费全文 | 2064篇 |
免费 | 139篇 |
出版年
2021年 | 11篇 |
2020年 | 7篇 |
2019年 | 10篇 |
2018年 | 19篇 |
2017年 | 16篇 |
2016年 | 14篇 |
2015年 | 41篇 |
2014年 | 38篇 |
2013年 | 122篇 |
2012年 | 87篇 |
2011年 | 81篇 |
2010年 | 56篇 |
2009年 | 54篇 |
2008年 | 112篇 |
2007年 | 119篇 |
2006年 | 113篇 |
2005年 | 112篇 |
2004年 | 139篇 |
2003年 | 96篇 |
2002年 | 106篇 |
2001年 | 71篇 |
2000年 | 74篇 |
1999年 | 61篇 |
1998年 | 27篇 |
1997年 | 32篇 |
1996年 | 22篇 |
1995年 | 34篇 |
1994年 | 33篇 |
1993年 | 25篇 |
1992年 | 54篇 |
1991年 | 53篇 |
1990年 | 57篇 |
1989年 | 21篇 |
1988年 | 47篇 |
1987年 | 28篇 |
1986年 | 25篇 |
1985年 | 24篇 |
1984年 | 16篇 |
1983年 | 16篇 |
1982年 | 14篇 |
1981年 | 11篇 |
1980年 | 8篇 |
1979年 | 13篇 |
1978年 | 6篇 |
1977年 | 7篇 |
1976年 | 11篇 |
1975年 | 8篇 |
1974年 | 16篇 |
1973年 | 7篇 |
1968年 | 6篇 |
排序方式: 共有2203条查询结果,搜索用时 15 毫秒
51.
Keith L. Constantine Mark S. Friedrichs David Detlefsen Maki Nishio Mitsuaki Tsunakawa Tamotsu Furumai Hiroaki Ohkuma Toshikazu Oki Susan Hill Robert E. Bruccoleri Pin-Fang Lin Luciano Mueller 《Journal of biomolecular NMR》1995,5(3):271-286
Summary The 21-amino acid peptides siamycin II (BMY-29303) and siamycin I (BMY-29304), derived from Streptomyces strains AA3891 and AA6532, respectively, have been found to inhibit HIV-1 fusion and viral replication in cell culture. The primary sequence of siamycin II is CLGIGSCNDFAGCGYAIVCFW. Siamycin I differs by only one amino acid; it has a valine residue at position 4. In both peptides, disulfide bonds link Cys1 with Cys13 and Cys7 with Cys19, and the side chain of Asp9 forms an amide bond with the N-terminus. Siamycin II, when dissolved in a 50:50 mixture of DMSO and H2O, yields NOESY spectra with exceptional numbers of cross peaks for a peptide of this size. We have used 335 NOE distance constraints and 13 dihedral angle constraints to generate an ensemble of 30 siamycin II structures; these have average backbone atom and all heavy atom rmsd values to the mean coordinates of 0.24 and 0.52 Å, respectively. The peptide displays an unusual wedge-shaped structure, with one face being predominantly hydrophobic and the other being predominantly hydrophilic. Chemical shift and NOE data show that the siamycin I structure is essentially identical to siamycin II. These peptides may act by preventing oligomerization of the HIV transmembrane glycoprotein gp41, or by interfering with interactions between gp41 and the envelope glycoprotein gp120, the cell membrane or membrane-bound proteins [Frèchet, D. et al. (1994) Biochemistry, 33, 42–50]. The amphipathic nature of siamycin II and siamycin I suggests that a polar (or apolar) site on the target protein may be masked by the apolar (or polar) face of the peptide upon peptide/protein complexation.Abbreviations ABNR
adopted basis Newton Raphson
- AIDS
acquired immunodeficiency syndrome
- CW
continuous wave
- DMSO
dimethylsulfoxide
- DQF-COSY
two-dimensional double-quantum-filtered correlation spectroscopy
- HIV
human immunodeficiency virus
- HSQC
heteronuclear single-quantum coherence
- NOE
nuclear Overhauser enhancement
- NOESY
two-dimensional nuclear Overhauser enhancement spectroscopy
- ppm
parts per million
- P.E.-COSY
two-dimensional primitive exclusive correlation spectroscopy
- REDAC
redundant dihedral angle constraint
- rf
radio frequency
- rmsd
root-mean-square difference
- SIV
simian immunodeficiency virus
- sw
spectral width
- m
mixing time
- TOCSY
two-dimensional total correlation spectroscopy
- TSP
trimethylsilyl-2,2,3,3-2H4-propionate
- 2D
two-dimensional 相似文献
52.
H. Ikezawa K. Tameishi A. Yamada H. Tamura K. Tsukamoto Y. Matsuo K. Nishikawa 《Amino acids》1995,9(3):293-298
Summary Chemical modifications suggested that acidic amino acids such as aspartic and glutamic acids are involved in the active sites ofBacillus cereus sphingomyelinase. Among aspartic acid residues in the conserved regions of this enzyme, Asp-126, Asp-156, Asp-233 and Asp-295 were converted to glycine by site-directed mutagenesis. According to prediction on structural similarity to pancreatic DNase I, His-151 and His-296 were also converted to alanine. The Asp and His mutants, D126G, D156G, D233G, D295G, H151A and H296A, were produced inBacillus brevis 47, a protein-hyperproducing strain. The catalytic activities of D295G, H151A and H296A were completely abolished, and sphingomyelin-hydrolyzing activity of D126G or D156G was reduced by more than 50%. The activity of D126G towardp-NPPC was comparable to that of the wild-type, while D156G catalyzed the hydrolysis of HNP andp-NPPC more efficiently than the wild-type. Hemolytic activities of the mutants were parallel to their sphingomyelin-hydrolyzing activities. 相似文献
53.
Yukio Takahata Toshikazu Hasegawa Toshisada Nishida 《International journal of primatology》1984,5(3):213-233
Fifty-four episodes of predatory behavior of wild chimpanzees were recorded in Mahale, western Tanzania, from August 1979
to May 1982. The chimpanzees most frequently hunt in two seasons, during May, and from August to December. Longer-term fecal
analysis indicates that predation frequency is significantly higher in the dry than in the rainy season. The seasonality of
predation might be the result of the sum of various ecological factors, at least one of which is the birth season of the prey
species. Most of the prey are juvenile blue duiker, bushbuck, bushpig, red colobus, and red-tailed monkeys. Sex difference
is recognized in the prey selection and in the hunting method employed. Apparent local difference in the predatory behavior
between Mahale and Combe chimpanzees (in Mahale,females hunt more frequently, and blue duiker is the most frequent prey) can be understood in terms of the difference either
in the observation methods or in the faunal diversity and density. Other aspects of predatory behavior also are reported. 相似文献
54.
Mariko Hiraiwa-Hasegawa Toshikazu Hasegawa Toshisada Nishida 《Primates; journal of primatology》1984,25(4):401-413
Long-term demographic observations on a large-sized unit-group of chimpanzees in the Mahale Mountains, Tanzania, are summarized.
The unit-group, the M group, contains over 100 individuals, which makes it the largest unit-group ever reported. The age-sex
composition, natality, mortality and transfers of the M group are analyzed. An attempt is made to illustrate an age-sex pyramid
of the group by estimating the ages of all the individuals in the group. The results reveal that: (1) the mortality rate of
the male infants within 1 year almost doubled that of female infant; (2) adult male to adult female ratio of the M group is
considerably higher than any other unit-groups elsewhere; and (3) the M group contains a relatively large number of old animals
over 40 years of age, suggesting that the longevity of wild chimpanzees might be greater than estimated so far. 相似文献
55.
Identification of single-stranded regions in Torulopsis utilis 5S RNA was attempted by the use of Nuclease S1, a single-strand specific endonuclease. When T. utilis 5S RNA was subjected to prolonged incubation with Nuclease S1, about 50% of the substrate 5S RNA remained as large oligonucleotide "cores." Such Nuclease S1-resistant fragments were purified and sequenced by column chromatographic procedures. These analyses revealed that regions around positions 12, 40, 57, and 110 are in exposed single-stranded loops at 37 degrees C and that regions around positions 12 and 40 are most exposed at 20 degrees C. These results are compatible with our secondary structure model for T. utilis 5S RNA (Nishikawa & Takemura (1974) J. Biochem. 76, 935-947) except that the 5' part of the molecule (from the region around position 22 to that around position 57) might have a somewhat looser conformation than our secondary structure model suggests. The implications of such results are also discussed in relation to the presumed function of the sequence C-G-A-U-C (around position 40) as one of the recognition sites for initiator tRNA binding on ribosomes. 相似文献
56.
Tatsunosuke Nakamura Masahiko Nishikawa Keizo Inoue Shoshichi Nojima Toshiyuki Akiyama Ushio Sankawa 《Chemistry and physics of lipids》1980,26(1):101-110
The effect of the length of the side chain of sterols on their interaction with phosphatidylcholine was studied by measuring the permeability properties of liposomes constituted with sterol analogues with side chains of various lengths. The sensitivities of liposomes constituted with these sterol analogues toward digitonin and polyene antibiotics were also examined.The effects of sterols on phase transition of phosphatidylcholine were examined by measuring their effects on permeability increase due to perturbation of phase equilibrium and by differential scanning calorimetry. An analogue with a short side chain, isopropyl (C-22), had a very similar effect to cholesterol in suppressing the permeability increase, suggesting that the full length of the side chain is not necessary for this effect.The permeability of egg yolk phosphatidylcholine at 42°C was suppressed as much by the analogue C-22 as by cholesterol. Androstene-3-β-ol, an analogue without a side chain, however, had little suppressive effect. Thus it is concluded that the condensing effect of sterol requires a side chain, but not the full length of side chain.Liposomes constituted with analogues having a side chain with more than 5 carbon atoms showed maximum reactivity with a polyene antibiotic, amphotericin B, whereas those constituted with analogues having a side chain with less than 4 carbon atoms showed weaker reactivity. These findings indicate that a side chain with more than 5 carbon atoms is essential for the maximum interaction of liposomes with amphotericin B. Unlike amphotericin B, filipin reacted almost equally well with liposomes containing C-22 and with those containing cholesterol. Thus the chain length of the side chain of sterol is less important for interaction of liposomes with filipin than for their interaction with amphotericin B.Liposomes containing analogues having a side chain with more than 6 carbon atoms showed maximum reactivity with digitonin. Thus for the maximum interaction of liposomes with digitonin, the side chain of sterol should be longer than 6 carbon atoms. 相似文献
57.
H Fushimi S Tsukuda T Hanafusa Y Matsuyuki M Nishikawa S Ishihara K Kanao 《Endocrinologia japonica》1980,27(6):679-687
Twenty five cases of insulin autoimmune syndrome including this case has been reported so far without having the pathogenesis clarified. This paper describes a case which suggests one aspect of pathogenesis. The patient, a housewife concurrently had insulinoma and severe rheumatoid arthritis, complaining of hypoglycemic syncope attacks. During the attacks her blood sugar levels ranged from 19 to 22 mg%. Her serum extractable immunoreactive insulin (IRI) and insulin binding antibody levels were 557 microunits/ml and 0.390 mU/ml, respectively. gamma-Globulin-bound insulin was also measured electrophoretically. Bio-Gel P 10 column chromatography eluted almost all IRI at the void volume at pH 7.4 and a smaller but significant IRI peak also at pH 3.0. Selective angiography revealed a tumor-like staining in the pancreas body. Pancreatectomy relieved her of hypoglycemic attacks. Histology disclosed two small insulinomas. Insulinoma, rheumatoid arthritis and insulin autoimmune syndrome coexisted in this case, suggesting some causal relationship among them. 相似文献
58.
Tadao Maeda Toshikazu Yamaguchi Masahisa Hashimoto 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1981,223(2):357-363
A gas chromatographic method has been developed that permits the accurate and specific determination of the hypoglycaemic agent gliclazide in plasma. Gliclazide is extracted with chloroform and, after clean-up, derivatized with diazomethane followed by heptafluorobutyric anhydride to form N-methyl-N′-heptafluorobutyrylgliclazide, which is assayed on a gas chromatograph equipped with a flame ionization detector, an electron-capture detector or a nitrogen—phosphorus sensitive detector.Accurate determinations are possible with flame ionization detection over a concentration range of 1–15 μg/ml of gliclazide in plasma with a relative standard deviation of 5.2%. The minimum detectable concentration with electron-capture detection is 0.02 μg per sample. Plasma levels of gliclazide in dogs following single oral administration (40 mg per dog) have also been determined. 相似文献
59.
Dye-coupled electrode system for the rapid determination of cell populations in polluted water. 总被引:7,自引:1,他引:6
下载免费PDF全文
![点击此处可从《Applied microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
We determined cell populations in polluted waters by using a fuel cell-type electrode. The electrode was constructed from a platinum anode, a silver peroxide cathode, and a membrane filter for retaining microorganisms. The principle of cell number determination is based on sensing a redox dye reduced by the microorganisms with the electrode. Sample solutions containing microorganisms were membrane filtered, and the resulting filter containing microbial cells was attached to the surface of a platinum anode. The electrode was immersed in phosphate buffer solution (0.05 M, pH 7) containing a redox dye (2,4-dichlorophenol-indophenol), and the current generated was measured. The response time of the electrode system was 10 to 20 min, and the current generated was proportional to cell populations above 10(4) cells/ml. 相似文献
60.
Correspondence of homologies in amino acid sequence and tertiary structure of protein molecules 总被引:7,自引:0,他引:7
According to the method developed previously (Kubota, Y., Takahashi, S., Nishikawa, K. and Ooi, T. (1981) J. Theor, Biol. 91, 347-361), homology among proteins may be estimated quantitatively. We extended the method to investigate the relationship of an amino acid sequence to its teritary structure and identify homologous segments which have homologous native conformations in proteins. First, we selected proper indices for the computation of correlation coefficients from 32 properties inherent to amino acids, such as hydrophobicity. The arithmetic average of correlation coefficients using six indices gave rise to a good correlation for the CD- and EF-hand regions (Ca2+ binding sites) in carp parvalbumin, but poor ones for other segments. We then applied the method to homologous proteins, the three-dimensional structures of which are known: horse hemoglobin alpha-chain and beta-chain; cytochrome c and c2; serine proteases, chymotrypsinogen and elastase; alpha-lytic protease and protease A from prokaryotic organisms. The results show that the sequence homology estimated by the present method has a good correspondence to the homology in three-dimensional structures and therefore the method is promising for the identification of important sites in sequences which have similar native conformations. For an example of the application of the method, two sequences of human interferon, one from fibroblast and the other from leukocyte, are compared, suggesting functional sites in the molecule. 相似文献