全文获取类型
收费全文 | 19217篇 |
免费 | 2840篇 |
国内免费 | 203篇 |
专业分类
22260篇 |
出版年
2023年 | 45篇 |
2022年 | 112篇 |
2021年 | 211篇 |
2020年 | 183篇 |
2019年 | 212篇 |
2018年 | 322篇 |
2017年 | 293篇 |
2016年 | 426篇 |
2015年 | 513篇 |
2014年 | 625篇 |
2013年 | 716篇 |
2012年 | 797篇 |
2011年 | 922篇 |
2010年 | 533篇 |
2009年 | 532篇 |
2008年 | 660篇 |
2007年 | 647篇 |
2006年 | 631篇 |
2005年 | 551篇 |
2004年 | 509篇 |
2003年 | 499篇 |
2002年 | 473篇 |
2001年 | 2283篇 |
2000年 | 2118篇 |
1999年 | 1484篇 |
1998年 | 428篇 |
1997年 | 448篇 |
1996年 | 380篇 |
1995年 | 350篇 |
1994年 | 262篇 |
1993年 | 221篇 |
1992年 | 717篇 |
1991年 | 587篇 |
1990年 | 499篇 |
1989年 | 389篇 |
1988年 | 307篇 |
1987年 | 240篇 |
1986年 | 179篇 |
1985年 | 136篇 |
1984年 | 85篇 |
1983年 | 65篇 |
1982年 | 44篇 |
1981年 | 41篇 |
1980年 | 26篇 |
1979年 | 30篇 |
1978年 | 27篇 |
1976年 | 30篇 |
1973年 | 30篇 |
1972年 | 24篇 |
1970年 | 24篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
101.
M. Jane Ehrke Richard L. X. Ho Kazuyoshi Hori 《Cancer immunology, immunotherapy : CII》1988,27(2):103-108
Summary Recombinant murine (rMu) tumor necrosis factor (TNF), in a standard comitogenic assay with phytohemagglutinin, induced murine thymocyte proliferation, while up to 10,000-fold higher concentrations of recombinant human TNF did not. The induction of thymocyte proliferation was dependent upon TNF concentration in a biphasic manner. Thus, 100 to 1000 units/ml TNF were near optimal while concentrations 1,000 units/ml caused apparent down regulation. The effect was abrogated by neutralizing antibody to rMu-TNF but not by neutralizing antibody to rMu-interleukin 1 or . The rMu-TNF did not induce proliferation of the mature murine T-helper cell line, D10.G4.1, in the presence of mitogen. Taken together the results indicate that TNF, in a strictly species-specific manner, can regulate thymocyte proliferation independently of interleukin 1.Supported in part by Asahi Chemical Industry Co., Inc. and by USPHS Grants CA-24538, CA-15142 and CA-09072 awarded by the National Cancer Institute, Department of Health and Human Services 相似文献
102.
Robert S. Aronstam Michael W. Edwards John W. Daly X. Albuquerque 《Neurochemical research》1988,13(2):171-176
The interactions of eight piperidine derivatives with nicotinic receptor complexes fromTorpedo californica electric organ were studied using [125I]alpha-bungarotoxin ([125I]BGT) as a probe for the acetylcholine binding site and [3H]perhydrohistrionicotoxin ([3H]H12-HTX) as a probe for a site associated with the receptor-gated ion channel.Cis- andtrans-2-methyl-6-n-undecanyl piperidines (MUP), major constituents of fire ant venom, had a high-affinity for [3H]H12-HTX binding sites (Ki=0.08–0.24 M), but had no affect on receptor binding. MUP affinity for [3H]H12-HTX binding sites was approximately doubled in the presence of 1 M carbamylcholine. Introduction of a 2-hydroxyl group to the undecanyl side channel had little effect on activity of the alkaloid. The analog 2,6- (but not 3,5-) dimethylpiperidine was a moderately active inhibitor of [3H]H12-HTX binding (K
i-8.8 M). 2-Methylpiperidine was considerably less active (K
i=600 M), although it was more potent than either 3- or 4-methylpiperidine. The affinities of 2,6-dimethylpiperidine and 2-methylpiperidine for [3H]H12-HTX binding sites were decreased in the presence of 1 M carbamylcholine. Carbamylcholine affinity for the receptor was increased by up to 7 fold in the presence of 10 and 32 M MUP, but was decreased in the presence of 2,6-dimethylpiperidine and 2-methylpiperidine. Thecis- andtrans-isomers of MUP were equipotent in producing each of its effects. In these actions, MUP resembles a variety of other compounds derived from 2,6-disubstituted piperidines, including histrionicotoxins, gephyrotoxins and pumiliotoxins. These studies establish the importance of alkyl substitutions in theortho position of the piperidine ring in conferring ion channel specificity, and the importance of substantial alkyl side chains in conferring the ability of channel blockers to stabilize the nicotinic receptor complex in high affinity, desensitized conformations. 相似文献
103.
H X Lin T Kleinschmidt G Braunitzer H G Scheil 《Biological chemistry Hoppe-Seyler》1988,369(5):349-355
The hemoglobin of the Common Otter (Lutra lutra, Carnivora) contains only one component. The complete primary structures of the alpha- and beta-chains are presented. They were separated by high-performance liquid chromatography and the sequences determined by automatic liquid and gas-phase Edman degradation of the chains and their tryptic peptides. The alpha-chains show 18 and the beta-chains 13 substitutions compared to human alpha- and beta-chains, respectively. In the alpha-chains one heme- and two alpha 1/beta 1-contacts are exchanged. In the beta-chains the replacements involve one heme-, one alpha 1/beta 1-, and one alpha 1/beta 2-contact. The alpha- and beta-chains of the Common Otter are compared to those of other Carnivora hemoglobins. The unexpected low number of substitutions between Common Otter hemoglobin and that of Lesser Panda as well as of Harbor Seal is discussed. 相似文献
104.
The presence of a binding site to (+)-(3H)SKF 10,047 was demonstrated in a guinea-pig myenteric plexus (MYP) membrane preparation. Specific binding to this receptor was saturable, reversible, linear with protein concentration and consisted of two components, a high affinity site (KD = 46 +/- 5 nM; Bmax = 3.4 +/- 0.5 pmole/g wet weight) and a low affinity site (KD= = 342 +/- 72 nM; Bmax = 22 +/- 3 pmole/g wet weight). Morphine and naloxone 10(-4) M were unable to displace (+)-(3H)SKF 10,047 binding. Haloperidol, imipramine, ethylketocyclazocine and propranolol were among the most potent compounds to inhibit this specific binding. These results suggest the presence of a non-opioid haloperidol sensitive sigma receptor in the MYP of the guinea-pig. 相似文献
105.
Hancai Chen James X. Gray Murali Nayudu Michael A. Djordjevic Michael Batley John W. Redmond Barry G. Rolfe 《Molecular & general genetics : MGG》1988,212(2):310-316
Summary R-prime plasmids were constructed from a derivative of Rhizobium strain NGR234 (ANU280) and were shown to contain overlapping genomic DNA segments involved in biosynthesis of exopolysaccharides (EPS). The R-primes originally constructed carried the mutant allele from Tn5-induced EPS-deficient (Exo–) mutant ANU2811. This plasmid-located mutant allele was dominant to the corresponding wild-type allele as merodiploid strains were Exo–. Exo+ revertants occurred at a low rate (1×10-7) and these were shown to result from double reciprocal recombination events, which led to the isolation of R-prime plasmids carrying functional wild-type exo alleles. R-prime plasmids that carry overlapping segments of DNA from parental strain ANU280 complemented 28 of the 30 group 2 Exo– mutants of strain ANU280. Complementation of these Exo– mutants also restored their symbiotic abilities of effective nodulation. Subsequent in vivo recombination between the wild-type alleles located on the R-prime and the corresponding mutated allele on the genome, was used to generate a new family of R-primes, which carried mutations in the exo genes. The 30 group 2 Exo– mutants were classified into 7 distinct genetic groups based upon complementation and physical mapping data. Five of the seven exo loci were gentically linked and located on a 15-kb region of DNA. Mutations at two loci were dominant only when the mutations were R-prime plasmid-located while a mutation at a second locus was cis-dominant to two other exo loci. At least five genes involved in the synthesis of acidic exopolysaccharide synthesis have been identified. 相似文献
106.
A developmentally regulated hydroxyproline-rich glycoprotein in maize pericarp cell walls 总被引:12,自引:3,他引:9
下载免费PDF全文
![点击此处可从《Plant physiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
We have studied the accumulation of peptidyl hydroxyproline in the pericarp of developing maize (Zea mays L., Golden cross Bantam sweet corn) kernels. Although this hydroxyproline accumulates throughout development, it is most soluble and its content per milligram dry weight greatest at midmaturation stages of development. Salt-soluble proteins containing this hydroxyproline from isolated cell walls of developing kernels were fractionated on a CsCl density gradient and on a Chromatofocusing column, resulting in the purification of an hydroxyproline-rich glycoprotein, PC-1. PC-1 is a basic protein of approximately 65 to 70 kilodaltons in molecular weight with an isoelectric point of at least 10.2 and a density of 1.38 to 1.39 in CsCl. Amino acid composition data indicate that it is rich in hydroxyproline, threonine, proline, lysine, and glycine. Its relation to dicot extensin is discussed. 相似文献
107.
Expression of an ouabain-resistant Na,K-ATPase in CV-1 cells after transfection with a cDNA encoding the rat Na,K-ATPase alpha 1 subunit 总被引:5,自引:0,他引:5
J R Emanuel J Schulz X M Zhou R B Kent D Housman L Cantley R Levenson 《The Journal of biological chemistry》1988,263(16):7726-7733
We have used a gene transfer system to investigate the relationship between expression of the rat Na,K-ATPase alpha 1 subunit gene and ouabain-resistant Na,K-ATPase activity. A cDNA clone encoding the entire rat Na,K-ATPase alpha 1 subunit was inserted into the expression vector pSV2neo. This construct (pSV2 alpha 1) conferred resistance to 100 microM ouabain to ouabain-sensitive CV-1 cells. Hybridization analysis of transfected clones revealed the presence of both rat-specific and endogenous Na,K-ATPase alpha 1 subunit DNA and mRNA sequences. A single form of highly ouabain-sensitive 86Rb+ uptake was detected in CV-1 cells, whereas two distinct classes of ouabain-inhibitable uptake were observed in transfectants. One class exhibited the high ouabain sensitivity of the endogenous monkey Na,K-ATPase, while the second class showed the reduced ouabain sensitivity characteristic of the rodent renal Na,K-ATPase. Examination of the ouabain-sensitive, sodium-dependent ATPase activity of the transfectants also revealed a low affinity component of Na,K-ATPase activity characteristic of the rodent kidney enzyme. These results suggest that expression of the rat alpha 1 subunit gene is directly responsible for ouabain-resistant Na,K-ATPase activity in transfected CV-1 cells. 相似文献
108.
Epitopes of an influenza viral peptide recognized by antibody at single amino acid resolution 总被引:6,自引:0,他引:6
P G Schoofs H M Geysen D C Jackson L E Brown X L Tang D O White 《Journal of immunology (Baltimore, Md. : 1950)》1988,140(2):611-616
Antibodies raised against the synthetic peptide corresponding to the carboxy-terminal 24 amino acids (305-328) of the heavy chain of the hemagglutinin molecule of influenza virus A/X-31 (H3) bind this peptide at three antigenic sites. These sites were identified by assaying binding of polyclonal BALB/c mouse antipeptide sera to the complete set of all possible di-, tri, tetra-, penta-, hexa-, hepta-, and octapeptides homologous with the 24-residue sequence. Individual epitopes were defined and essential residues identified by testing the binding of monoclonal antibodies to sets of peptide analogues in which every one of the homologous residues was replaced in turn by each of the 19 alternative genetically coded amino acids. The immunodominant epitope was shown to be a linear sequence of five amino acids, 314LKLAT318. Replacement of any one of these residues with any other amino acid resulted in loss of antibody binding, indicating that all five are essential to the interaction and that they are probably contact residues. Another antigenic site contains at least two overlapping epitopes: polyclonal sera recognize predominantly an epitope or epitopes encompassed by the linear sequence 320MRNVPEKQT328, whereas the epitope defined by a particular monoclonal antibody comprises the seven amino acids 322NVPEKQT328, of which N322, E325, and Q327 were implicated as contact residues. 相似文献
109.
X Bertagna F Camus F Lenne F Girard J P Luton 《Molecular endocrinology (Baltimore, Md.)》1988,2(11):1108-1114
The human (h) POMC gene sequence predicts a 30 amino acid joining peptide (JP) separating the N-terminal fragment [POMC(1-76) or hNT] and ACTH within their common precursor. We used an anti-serum directed against the amidated COOH-terminal end of mouse JP to develop a RIA for the predicted hJP molecule. Immunoreactive JP was detected in tissue extracts from human normal pituitary, ACTH-secreting pituitary- and nonpituitary tumors, and in plasma from patients with ACTH hypersecretory syndromes. Its molar concentration was of the same order of magnitude as, and correlated with, that of the other POMC peptides. Gel exclusion chromatography in 1% formic acid and 6 M guanidine-HCl revealed a predominant immunoreactive material with an apparent mol wt of ca. 6000. After reduction with dithiothreitol this material was recovered in an elution volume identical to that of purified hJP and corresponding to a mol wt of ca. 3000. These data show that POMC processing generates a COOH terminally amidated hJP predominantly secreted as a homodimer, probably through disulfide bonding between the single Cys9 residue of two molecules. 相似文献
110.
A cell type-specific enhancer drives expression of the chick muscle acetylcholine receptor alpha-subunit gene 总被引:14,自引:0,他引:14
The regulation of acetylcholine receptor alpha-subunit gene expression was analyzed by transient expression assays. Using rabbit beta-globin cDNA as a reporter gene, we have confirmed that the 5'-flanking sequence of the chicken acetylcholine receptor alpha-subunit gene directs specific expression in differentiated C2C12 cells, a mouse muscle cell line, but not in undifferentiated C2C12 cells and mouse 3T3 fibroblasts. Testing chimeric plasmids containing Bal31 deletion mutants of the alpha-subunit gene upstream sequence, we found the -116 to -81 region of the alpha-subunit to be responsible for tissue- and stage-specific expression. This 36 bp fragment stimulates the activity of both alpha-subunit and SV40 promoters in a distance- and orientation-independent manner, thus fulfilling the criteria of an enhancer. 相似文献