全文获取类型
收费全文 | 3224篇 |
免费 | 328篇 |
出版年
2022年 | 30篇 |
2021年 | 49篇 |
2020年 | 41篇 |
2019年 | 47篇 |
2018年 | 50篇 |
2017年 | 50篇 |
2016年 | 96篇 |
2015年 | 176篇 |
2014年 | 162篇 |
2013年 | 197篇 |
2012年 | 245篇 |
2011年 | 234篇 |
2010年 | 177篇 |
2009年 | 96篇 |
2008年 | 173篇 |
2007年 | 165篇 |
2006年 | 144篇 |
2005年 | 135篇 |
2004年 | 144篇 |
2003年 | 100篇 |
2002年 | 95篇 |
2001年 | 57篇 |
2000年 | 83篇 |
1999年 | 63篇 |
1998年 | 29篇 |
1997年 | 22篇 |
1996年 | 22篇 |
1995年 | 17篇 |
1994年 | 20篇 |
1993年 | 30篇 |
1992年 | 37篇 |
1991年 | 38篇 |
1990年 | 36篇 |
1989年 | 28篇 |
1988年 | 26篇 |
1987年 | 19篇 |
1986年 | 20篇 |
1985年 | 20篇 |
1984年 | 26篇 |
1983年 | 24篇 |
1982年 | 22篇 |
1981年 | 19篇 |
1979年 | 18篇 |
1978年 | 14篇 |
1977年 | 19篇 |
1974年 | 16篇 |
1973年 | 22篇 |
1972年 | 17篇 |
1969年 | 23篇 |
1968年 | 12篇 |
排序方式: 共有3552条查询结果,搜索用时 281 毫秒
61.
Murthy PP Pliska-Matyshak G Keranen LM Lam P Mueller HH Bhuvarahamurthy N 《Plant physiology》1992,98(4):1498-1501
The structure of phosphatidylinositol in barley (Hordeum vulgare) aleurone layers was investigated by chemical degradation. In vivo myo-[2-3H]inositol-labeled phosphatidylinositol was first converted to glycerophosphoinositol and, subsequently, after removal of the glycerol moiety, to inositol monophosphate. Here, we present data that show that, in addition to the commonly occurring 1,2-diacylglycero-3-(d-myo-inositol-1-phosphate), barley aleurone cells contain a novel second isomer of phosphatidylinositol that differs in structure of the head group. 相似文献
62.
63.
T A Butler C Zhu R A Mueller G C Fuller W J Lemaire J F Woessner 《Biology of reproduction》1991,44(6):1183-1188
A new, powerful, synthetic inhibitor of mammalian tissue collagenases and related metalloproteinases is inhibitory to ovulation in perfused rat ovaries. Ovaries of immature rats, primed with 20 IU of eCG, were dissected and perfused with 0.1 micrograms/ml LH and 0.2 mM 3-isobutyl-1-methylxanthine (IBMX) for 20 h. Addition of SC 44463 (N4-hydroxy-N1-[1S [(4-methoxphenyl)methyl]-2-(methylamino)-2-oxoethyl]- 2R-(2-methylpropyl)butane-diamide) at a concentration of 25 nM inhibited ovulation by 55% (9.6 +/- 1.7 ovulations per ovary, mean +/- SEM, compared to a control value of 21.7 +/- 1.7); and 250 nM inhibited ovulation by 75% (5.3 +/- 1.1 ovulations per ovary). We previously showed that the related compound SC 40827 inhibited ovulation by 70% when used at a concentration of 25 microM (Br?nnstr?m et al., Endocrinology 1988; 122:1715-1721). We now show that SC 44463 is 100, 500, and 75 times more powerful than SC 40827 in blocking ovulation, inhibiting action of ovarian interstitial collagenase, and inhibiting action of the small metalloproteinase of the rat uterus, respectively. SC 44463 also inhibits ovarian type IV collagen-digesting activity 50% at a concentration of 18 nM. Ovulation occurs after 9-12 h of perfusion with LH. Compound SC 44463 (25 nM) showed its full inhibitory capacity when added to the medium as late as 7 h after LH, but there was no significant inhibition when it was added at 9 h. This suggests that the major collagenolytic events occur beyond 7 h after stimulation by LH. 相似文献
64.
S J Usala J B Menke T L Watson F E Wondisford B D Weintraub J Bérard W E Bradley S Ono O T Mueller B B Bercu 《Molecular endocrinology (Baltimore, Md.)》1991,5(3):327-335
Different point mutations have been identified in the T3-binding domain of the c-erbA beta thyroid hormone receptor gene that are associated with variant phenotypes of generalized thyroid hormone resistance (GTHR). In most cases of GTHR, heterozygotes are affected; a single mutant allele results in the inhibition of the function of normal thyroid hormone receptors. We report here a novel genetic abnormality, a 3-basepair (bp) deletion in the T3-binding domain of the beta-receptor in a kindred, S, with GTHR. One patient, S1, was the product of a consanguineous union of two heterozygotes and was homozygous for this defect. Heterozygotes from kindred S harbored a CAC deletion at nucleotides 1295-1297, which resulted in the deduced loss of amino acid residue threonine at codon 332, and they displayed elevated free T4 levels and inappropriately normal TSH levels characteristic of other kindreds with GTHR. However, patient S1, who had two mutant alleles, had markedly elevated TSH and free T4 levels and displayed profound abnormalities in brain development and linear growth. A fibroblast c-erbA beta cDNA extending from codon 175 to stop codon 457 was cloned from patient S1, sequenced, and used to create a full-length mutant cDNA. The kindred S mutant receptor was synthesized in vitro and did not bind T3. This mutant receptor did bind with similar avidity as the wild-type human beta-receptor to thyroid hormone response elements of the human TSH beta (-12 to 43 bp) and rat GH (-188 to -160 bp) genes. Kindred S showed the effect in man of heterozygous and homozygous expression of a dominant negative form of c-erbA beta. 相似文献
65.
The alpha subunit of type II Ca2+/calmodulin-dependent protein kinase is highly conserved in Drosophila 总被引:2,自引:0,他引:2
A monoclonal antibody against rat brain type II Ca2+/calmodulin-dependent protein kinase (CaM kinase) precipitates three proteins from Drosophila heads with apparent molecular weights similar to those of the subunits of the rat brain kinase. Fly heads also contain a CaM kinase activity that becomes partially independent of Ca2+ after autophosphorylation, as does the rat brain kinase. We have isolated a Drosophila cDNA encoding an amino acid sequence that is 77% identical to the sequence of the rat alpha subunit. All known autophosphorylation sites are conserved, including the site that controls Ca(2+)-independent activity. The gene encoding the cDNA is located between 102E and F on the fourth chromosome. The protein product of this gene is expressed at much higher levels in the fly head than in the body. Thus, both the amino acid sequence and the tissue specificity of the mammalian kinase are highly conserved in Drosophila. 相似文献
66.
Resolution of Holliday junction analogs by T4 endonuclease VII can be directed by substrate structure 总被引:3,自引:0,他引:3
J E Mueller C J Newton F Jensch B Kemper R P Cunningham N R Kallenbach N C Seeman 《The Journal of biological chemistry》1990,265(23):13918-13924
Endonuclease VII is an enzyme from bacteriophage T4 capable of resolving four-arm Holliday junction intermediates in recombination. Since natural Holliday junctions have homologous (2-fold) sequence symmetry, they can branch migrate, creating a population of substrates that have the branch point at different sites. We have explored the substrate requirements of endonuclease VII by using immobile analogs of Holliday junctions that lack this homology, thereby situating the branch point at a fixed site in the molecule. We have found that immobile junctions whose double-helical arms contain fewer than nine nucleotide pairs do not serve as substrates for resolution by endonuclease VII. Scission of substrates with 2-fold symmetrically elongated arms produces resolution products that are a function of the particular arms that are lengthened. We have confirmed that the scission products are those of resolution, rather than nicking of individual strands, by using shamrock junction molecules formed from a single oligonucleotide strand. A combination of end-labeled and internally labeled shamrock molecules has been used to demonstrate that all of the scission is due to coordinated cleavage of DNA on opposite sides of the junction, 3' to the branch point. Endonuclease VII is known to cleave the crossover strands of Holliday junctions in this fashion. The relationship of the long arms to the cleavage direction suggests that the portion of the enzyme which requires the minimum arm length interacts with the pair of arms containing the 3' portion of the crossover strands on the bound surface of the antiparallel junction. 相似文献
67.
NMR identification of protein surfaces using paramagnetic probes 总被引:5,自引:0,他引:5
Paramagnetic agents produce line broadening and thus cancellation of anti phase cross-peak components in two-dimensional correlated nuclear magnetic resonance spectra. The specificity of this effect was examined to determine its utility for identifying surface residues of proteins. Ubiquitin and hen egg white lysozyme, for which X-ray crystal structures and proton NMR assignments are available, served as test cases. Two relaxation reagents were employed, 4-hydroxy-2,2,6,6-tetramethylpiperidinyl-1-oxy and the gadolinium (III) diethylenetriaminepentaacetate complex ion. Correlations were sought between reagent-produced decreases of side-chain cross-peak volumes in double-quantum-filtered proton correlation (DQF-COSY) spectra and the solvent-exposed side-chain surface area of the corresponding residues. The lanthanide complex produced strong effects ascribable to association with carboxylate groups but was not otherwise useful in delineating surface residues. The nitroxyl, on the other hand, produced clear distinctions among the Val, Leu, and Ile residues that generally paralleled side-chain exposure in the crystal, although consistent correlations were not observed with residues of other types. Although an instance of possible specific protein-nitroxyl association was noted, the nitroxyl appears to be a tool for identifying hydrophobic surface residues. 相似文献
68.
R Weingarten L Ransn?s H Mueller L A Sklar G M Bokoch 《The Journal of biological chemistry》1990,265(19):11044-11049
Mastoparan, a peptide toxin from wasp venom, stimulates guanine nucleotide binding and hydrolysis by G proteins. To elucidate the site of mastoparan-G protein interaction, we utilized a polyclonal antibody (R16,17) directed against the carboxyl terminus of the Gi alpha subunit to develop a competitive enzyme-linked immunosorbent assay. We investigated the ability of mastoparan to influence R16,17 antibody binding to G protein alpha subunits in a purified preparation of brain Gi and in neutrophil membrane extracts. Mastoparan antagonized the ability of R16,17 to detect G protein alpha subunits with an IC50 of 15 microM in the purified preparation and with an IC50 of 1 microM for the predominant G protein population in membrane extracts. This reduction was not seen when an unrelated peptide or a peptide of similar charge composition to mastoparan was used in place of mastoparan in the assay. Additionally, antibody R16,17 blocked up to 85% of mastoparan-stimulated GTPase activity. Taken together, these data indicate that the interaction of mastoparan with G protein depends in part on the carboxyl terminus of Gi alpha. Pertussis toxin-catalyzed ADP-ribosylation of Gi alpha markedly inhibited mastoparan-stimulated GTPase activity but only slightly attenuated the ability of mastoparan to recognize G protein. These data suggest that ribosylation inhibits mastoparan-induced G protein activation by a mechanism distinct from the ability of mastoparan to physically interact with G protein. Since mastoparan is thought to mimic hormone-liganded receptors, these findings may be applicable to the mechanism of receptor-Gi protein uncoupling that results from ADP-ribosylation of the G protein. 相似文献
69.
70.
A protein with multiple heme-binding sites from rabbit serum 总被引:1,自引:0,他引:1
A 93,000 molecular weight protein (HBP.93) which binds hemin and protoporphyrin IX with high affinity has been isolated from rabbit serum using affinity chromatography on hemin-conjugated agarose. The amino acid composition of this protein is unique in that the proline and histidine contents are remarkably high (16.6 and 9.9 mol %, respectively). A large increase in the absorbance of the Soret region arises from the heme-protein interaction. The spectrophotometric titration showed that the protein can bind 25-35 mol of hemin/mol of protein. The apparent dissociation constant was estimated to be 1-4 X 10(-7) M for hemin at pH 7.4 and approximately 10(-6) M for protoporphyrin IX at pH 9.2. The similarity of the difference spectrum of heme-HBP.93 complex to that of heme-hemopexin complex suggests that a bisimidazol-type coordination of heme iron is involved in the binding. The extremely high capacity of HBP.93 to bind heme is also demonstrated by a large increase in the sedimentation velocity of the protein upon heme binding. The native heme-protein complex migrates faster than the heme-free protein in a polyacrylamide gel at pH 8.8; the increased mobility appears to be due to the charge on the carboxyl groups of the bound heme. Although the use of a hemin-agarose column has failed to reveal a protein of similar size and heme affinity in the sera of a number of other species, including man, the heme-binding properties and high histidine level of the human alpha 2-histidine-rich glycoprotein raise the possibility that the two proteins are related. 相似文献