全文获取类型
收费全文 | 22678篇 |
免费 | 2069篇 |
国内免费 | 3507篇 |
专业分类
28254篇 |
出版年
2024年 | 102篇 |
2023年 | 362篇 |
2022年 | 763篇 |
2021年 | 1148篇 |
2020年 | 847篇 |
2019年 | 1017篇 |
2018年 | 991篇 |
2017年 | 736篇 |
2016年 | 1046篇 |
2015年 | 1378篇 |
2014年 | 1617篇 |
2013年 | 1735篇 |
2012年 | 2163篇 |
2011年 | 1929篇 |
2010年 | 1266篇 |
2009年 | 1120篇 |
2008年 | 1383篇 |
2007年 | 1268篇 |
2006年 | 1191篇 |
2005年 | 1014篇 |
2004年 | 800篇 |
2003年 | 720篇 |
2002年 | 644篇 |
2001年 | 489篇 |
2000年 | 414篇 |
1999年 | 362篇 |
1998年 | 222篇 |
1997年 | 164篇 |
1996年 | 133篇 |
1995年 | 134篇 |
1994年 | 93篇 |
1993年 | 84篇 |
1992年 | 102篇 |
1991年 | 114篇 |
1990年 | 101篇 |
1989年 | 72篇 |
1988年 | 64篇 |
1987年 | 63篇 |
1986年 | 47篇 |
1985年 | 58篇 |
1984年 | 30篇 |
1983年 | 31篇 |
1982年 | 31篇 |
1981年 | 16篇 |
1979年 | 21篇 |
1978年 | 16篇 |
1977年 | 19篇 |
1976年 | 15篇 |
1975年 | 15篇 |
1972年 | 16篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
41.
A human protein selected for interference with Ras function interacts directly with Ras and competes with Raf1. 总被引:13,自引:8,他引:5 下载免费PDF全文
The overexpression of some human proteins can cause interference with the Ras signal transduction pathway in the yeast Saccharomyces cerevisiae. The functional block is located at the level of the effector itself, since these proteins do not suppress activating mutations further downstream in the same pathway. We now demonstrate, with in vivo and in vitro experiments, that the protein encoded by one human cDNA (clone 99) can interact directly with yeast Ras2p and with human H-Ras protein, and we have named this gene rin1 (Ras interaction/interference). The interaction between Ras and Rin1 is enhanced when Ras is bound to GTP. Rin1 is not able to interact with either an effector mutant or a dominant negative mutant of H-Ras. Thus, Rin1 displays a human H-Ras interaction profile that is the same as that seen for Raf1 and yeast adenylyl cyclase, two known effectors of Ras. Moreover, Raf1 directly competes with Rin1 for binding to H-Ras in vitro. Unlike Raf1, however, the Rin1 protein resides primarily at the plasma membrane, where H-Ras is localized. These data are consistent with Rin1 functioning in mammalian cells as an effector or regulator of H-Ras. 相似文献
42.
43.
44.
The crystal structure of cholestanyl n-octanoate (caprylate) (C35H62O2) is monoclinic with space group A2 and cell dimensions a = 10.103(7), b = 7.646(7), c = 87.63(7) A, beta = 90.51(6) degrees; Z = 8 [two molecules (A, B) in asymmetric unit], V = 6769 A3, Dc = 1.010 g cm-3. Integrated X-ray intensities for 3798 reflections with I greater than 2 sigma (I) were measured with a rotating anode diffractometer at room temperature. The structure was determined using direct methods. Block diagonal least squares refinement gave R = 0.111. Molecules A and B have almost fully extended conformations, but differ significantly in the rotation about the ester bond and in the C17 chains. The molecular packing in the crystal structure of cholestanyl caprylate consists of stacked bilayers each having d002 = 43.8 A in thickness and within each bilayer, cholestanols pack with cholestanols and caprylate chains pack with caprylate chains. The crystal structure is very similar to that of cholesteryl myristate but is quite different from that of cholesteryl caprylate. The phase equilibria of the cholestanyl caprylate/cholesteryl caprylate binary system have been shown to involve limited mutual solubility of the two components and to have a eutectic point at 73% cholestanyl caprylate. The cholesteric mesophase is monotropic at all compositions except for a narrow range near the eutectic point where it is enantiotropic. 相似文献
45.
46.
The solubility of inclusion proteins from Bacillus thuringiensis is dependent upon protoxin composition and is a factor in toxicity to insects. 总被引:8,自引:4,他引:4 下载免费PDF全文
Bacillus thuringiensis subsp. aizawai HD133 is one of several strains particularly effective against Plodia interpunctella selected for resistance to B. thuringiensis subsp. kurstaki HD1 (Dipel). B. thuringiensis subsp. aizawai HD133 produces inclusions containing three protoxins, CryIA(b), CryIC, and CryID, and the CryIC protoxin has been shown to be active on resistant P. interpunctella as well as on Spodoptera larvae. The CryIA(b) protoxin is very similar to the major one in B. thuringiensis subsp. kurstaki HD1, and as expected, this protoxin was inactive on resistant P. interpunctella. A derivative of B. thuringiensis subsp. aizawai HD133 which had been cured of a 68-kb plasmid containing the cryIA(b) gene produced inclusions comprising only the CryIC and CryID protoxins. Surprisingly, these inclusions were much less toxic for resistant P. interpunctella and two other Lepidoptera than those produced by the parental strain, whereas the soluble protoxins from these strains were equally effective. In contrast, inclusions from the two strains were about as active as soluble protoxins for Spodoptera frugiperda larvae, so toxicity differences between inclusions may be due to the solubilizing conditions within particular larval guts. Consistent with this hypothesis, it was found that a higher pH was required to solubilize protoxins from inclusions from the plasmid-cured strain than from B. thuringiensis subsp. aizawai HD133, a difference which is probably attributable to the absence of the CryIA(b) protoxin in the former. The interactions of structurally related protoxins within an inclusion are probably important for solubility and are thus another factor in the effectiveness of B. thuringiensis isolates for particular insect larvae. 相似文献
47.
In vivo inhibition of megakaryocyte and platelet production by platelet factor 4 in mice. 总被引:1,自引:0,他引:1
Z C Han S Bellucci E Bodevin H Y Wan Z X Shen J P Caen 《Comptes rendus de l'Académie des sciences. Série III, Sciences de la vie》1991,313(12):553-558
The in vivo effect of human platelet factor 4 (PF4) on murine megakaryocytopoiesis and thrombopoiesis was studied. Administration of PF4 induced a dose-dependent decrease in the numbers of megakaryocytes and their progenitor cells (CFU-MK), continuing for 1 week after the injection. However, the size of megakaryocytes and their colonies was not changed following PF4 injection. Platelet levels were significantly decreased at days 3-4. The number of CFU-GM was decreased at days 1-2. White blood cells and hemoglobin were unaffected by PF4. These data indicate that PF4 inhibits megakaryocyte and platelet production in vivo by acting on the early stage of megakaryocyte development. 相似文献
48.
Enzyme I of the bacterial phosphoenolpyruvate:glycose phosphotransferase system (PTS) exhibits a temperature-dependent monomer/dimer equilibrium. The accompanying paper (Han, M. K., Roseman, S., and Brand, L. (1990) J. Biol. Chem. 265, 1985-1995) shows that the C-terminal -SH residue (Cys-575) can be modified specifically with fluorescent probes such as pyrene maleimide. The derivative retains full enzyme activity, and is capable of forming dimers at room temperature. In the present studies, Enzyme I labeled in this way is found to exhibit a temperature-, concentration-, and pH-dependent monomer/dimer association. The kinetics of dimer formation of Enzyme I is measured in the following way. A derivatized Enzyme I sample is prepared with a pyrene moiety irreversibly attached to the C-terminal -SH residue and 5,5'-dithiobis-2-nitrobenzoic acid reversibly attached to the other 3 -SH residues. This modified enzyme does not form dimers at room temperature. Addition of dithiothreitol results in total release of the thionitrobenzoate anion within 2 min. After the three -SH groups are unblocked, steady-state and nanosecond time-resolved emission anisotropy measurements indicate the dimer is formed over a period of 30 min. In a similar experiment, little dimer formation is observed at 3 degrees C, at temperature at which the native enzyme also does not form dimers. Tryptophan fluorescence is also examined during the release of the thionitrobenzoate. After the completion of thionitrobenzoate release, additional slow steady-state tryptophan fluorescence changes are observed. These results suggest that dimer formation may be preceded by a conformational change following thionitrobenzoate release. 相似文献
49.
P G Pearson J G Slatter M S Rashed D H Han M P Grillo T A Baillie 《Biochemical and biophysical research communications》1990,166(1):245-250
S-(N-methylcarbamoyl)glutathione, a chemically-reactive glutathione conjugate, has been isolated from the bile of rats administered methyl isocyanate and characterized, as its N-benzyloxycarbonyl dimethylester derivative, by tandem mass spectrometry. The ability of this glutathione adduct to donate an N-methylcarbamoyl moiety to the free -SH group of cysteine was evaluated in vitro with the aid of a highly specific thermospray LC/MS assay procedure. The glutathione adduct reacted readily with cysteine in buffered aqueous media (pH 7.4, 37 degrees C) and after 2 hr, 42.5% of the substrate existed in the form of S-(N-methylcarbamoyl)cysteine. The reverse reaction, i.e. between the cysteine adduct and free glutathione, also took place readily under these conditions. It is concluded that conjugation of methyl isocyanate with glutathione in vivo affords a reactive S-linked product which displays the potential to carbamoylate nucleophilic amino acids. The various systemic toxicities associated with exposure of animals or humans to methyl isocyanate could therefore be due to release of the isocyanate from its glutathione conjugate, which thus may serve as a vehicle for the transport of methyl isocyanate in vivo. 相似文献
50.
T Oka S H Kweon M Ito J P Han T Fujii Y Natori 《Biochemical and biophysical research communications》1990,166(2):973-977
RNA synthesis in the nuclei of liver from newly hatched chicks was enhanced 1.25 fold at 10 min after intragastric administration of water. Differential inhibition of RNA synthesis by alpha-amanitin indicated that the enhancement mainly represented rRNA synthesis; the synthesis of mRNA and tRNA was scarcely affected. Enhanced RNA synthesis was accompanied by greater susceptibility of nuclei to digestion by micrococcal nuclease, indicating that the chromatin structure was modified. It was further shown that the "water effect" was mimicked by distention of the stomach by raising the pressure in the intragastric balloon. Since the prior administration of atropine abolished the "water effect", the enhancement of hepatic RNA synthesis may be mediated by hepatic nervous system. 相似文献