全文获取类型
收费全文 | 8560篇 |
免费 | 771篇 |
国内免费 | 3篇 |
出版年
2024年 | 7篇 |
2023年 | 42篇 |
2022年 | 89篇 |
2021年 | 155篇 |
2020年 | 119篇 |
2019年 | 163篇 |
2018年 | 157篇 |
2017年 | 157篇 |
2016年 | 248篇 |
2015年 | 477篇 |
2014年 | 464篇 |
2013年 | 524篇 |
2012年 | 760篇 |
2011年 | 737篇 |
2010年 | 401篇 |
2009年 | 395篇 |
2008年 | 579篇 |
2007年 | 522篇 |
2006年 | 526篇 |
2005年 | 507篇 |
2004年 | 491篇 |
2003年 | 419篇 |
2002年 | 381篇 |
2001年 | 108篇 |
2000年 | 70篇 |
1999年 | 90篇 |
1998年 | 96篇 |
1997年 | 73篇 |
1996年 | 61篇 |
1995年 | 52篇 |
1994年 | 65篇 |
1993年 | 32篇 |
1992年 | 37篇 |
1991年 | 35篇 |
1990年 | 27篇 |
1989年 | 23篇 |
1988年 | 24篇 |
1987年 | 19篇 |
1986年 | 21篇 |
1985年 | 15篇 |
1984年 | 27篇 |
1983年 | 17篇 |
1982年 | 17篇 |
1981年 | 16篇 |
1980年 | 10篇 |
1978年 | 12篇 |
1977年 | 9篇 |
1976年 | 6篇 |
1975年 | 8篇 |
1973年 | 11篇 |
排序方式: 共有9334条查询结果,搜索用时 0 毫秒
91.
The genes encoding the peripheral cannabinoid receptor and alpha-L-fucosidase are located near a newly identified common virus integration site, Evi11. 总被引:2,自引:0,他引:2 下载免费PDF全文
P J Valk S Hol Y Vankan J N Ihle D Askew N A Jenkins D J Gilbert N G Copeland N J de Both B Lwenberg R Delwel 《Journal of virology》1997,71(9):6796-6804
A new common region of virus integration, Evi11, has been identified in two retrovirally induced murine myeloid leukemia cell lines, NFS107 and NFS78. By interspecific backcross analysis, it was shown that Evi11 is located at the distal end of mouse chromosome 4, in a region that shows homology with human 1p36. The genes encoding the peripheral cannabinoid receptor (Cnr2) and alpha-L-fucosidase (Fuca1) were identified near the integration site by using a novel exon trapping system. Cnr2 is suggested to be the target gene for viral interference in Evi11, since proviruses are integrated in the first intron of Cnr2 and retroviral integrations alter mRNA expression of Cnr2 in NFS107 and NFS78. In addition, proviral integrations were demonstrated within the 3' untranslated region of Cnr2 in five independent newly derived CasBrM-MuLV (mouse murine leukemia virus) tumors, CSL13, CSL14, CSL16, CSL27, and CSL97. The Cnr2 gene encodes a seven-transmembrane G-protein-coupled receptor which is normally expressed in hematopoietic tissues. Our data suggest that the peripheral cannabinoid receptor gene might be involved in leukemogenesis as a result of aberrant expression of Cnr2 due to retroviral integration in Evi11. 相似文献
92.
Hybertson Brooks M.; Bursten Stuart L.; Leff Jonathan A.; Lee Young M.; Jepson Eric K.; Dewitt Chris R.; Zagorski John; Cho Hyun G.; Repine John E. 《Journal of applied physiology》1997,82(1):226-232
Hybertson, Brooks M., Stuart L. Bursten, Jonathan A. Leff,Young M. Lee, Eric K. Jepson, Chris R. Dewitt, John Zagorski, Hyun G. Cho, and John E. Repine. Lisofylline prevents leak, but not neutrophil accumulation, in lungs of rats given IL-1intratracheally. J. Appl. Physiol.82(1): 226-232, 1997.Interleukin-1 (IL-1) is increased in lunglavages from patients with the acute respiratory distress syndrome, andadministering IL-1 intratracheally causes neutrophil accumulation and aneutrophil-dependent oxidative leak in lungs of rats. In the presentstudy, we found that rats pretreated intraperitoneally with lisofylline[(R)-1-(5-hydroxyhexyl)-3,7-dimethylxanthine (LSF)], an inhibitor of lysophosphatidic acid acyl transferase, which reduces the production of unsaturated phosphatidic acid species,did not develop the lung leak or the related ultrastructural abnormalities that occur after intratracheal administration of IL-1.However, rats pretreated with LSF and then given IL-1 intratracheally did develop the same elevations of lung lavage cytokine-induced neutrophil chemoattractant (CINC) levels and the same increased numbersof lung lavage neutrophils as rats given IL-1 intratracheally. Lungs ofrats given IL-1 intratracheally also had increased unsaturated phosphatidic acid and free acyl (linoleate, linolenate) concentrations compared with untreated rats, and these lipid responses were prevented by pretreatment with LSF. Our results reveal that LSF decreases lungleak and lung lipid alterations without decreasing neutrophil accumulation or lung lavage CINC increases in rats given IL-1 intratracheally. 相似文献
93.
Evidence for Linkage of Bipolar Disorder to Chromosome 18 with a Parent-of-Origin Effect 总被引:16,自引:8,他引:8 下载免费PDF全文
O. Colin Stine Jianfeng Xu Rebecca Koskela Francis J. McMahon Michele Gschwend Carl Friddle Chris D. Clark Melvin G. McInnis Sylvia G. Simpson Theresa S. Breschel Eva Vishio Kelly Riskin Harriet Feilotter Eugene Chen Susan Shen Susan Folstein Deborah A. Meyers David Botstein Thomas G. Marr J. Raymond DePaulo 《American journal of human genetics》1995,57(6):1384-1394
A susceptibility gene on chromosome 18 and a parent-of-origin effect have been suggested for bipolar affective disorder (BPAD). We have studied 28 nuclear families selected for apparent unilineal transmission of the BPAD phenotype, by using 31 polymorphic markers spanning chromosome 18. Evidence for linkage was tested with affected-sib-pair and LOD score methods under two definitions of the affected phenotype. The affected-sib-pair analyses indicated excess allele sharing for markers on 18p within the region reported previously. The greatest sharing was at D18S37: 64% in bipolar and recurrent unipolar (RUP) sib pairs (P = .0006). In addition, excess sharing of the paternally, but not maternally, transmitted alleles was observed at three markers on 18q: at D18S41, 51 bipolar and RUP sib pairs were concordant for paternally transmitted alleles, and 21 pairs were discordant (P = .0004). The evidence for linkage to loci on both 18p and 18q was strongest in the 11 paternal pedigrees, i.e., those in which the father or one of the father's sibs is affected. In these pedigrees, the greatest allele sharing (81%; P = .00002) and the highest LOD score (3.51; θ = 0.0) were observed at D18S41. Our results provide further support for linkage of BPAD to chromosome 18 and the first molecular evidence for a parent-of-origin effect operating in this disorder. The number of loci involved, and their precise location, require further study. 相似文献
94.
Omar Benzakour Chryso Kanthou Florea Lupu Ulla Dennehy Chris Goodwin Michael F. Scully Vijay V. Kakkar David N. Cooper 《Journal of cellular biochemistry》1995,59(4):514-528
Thrombin is a potent mitogen for human vascular smooth muscle cells (HVSMC) and its enzymatic activity is required for this function. The present study demonstrates that prothrombin is also mitogenic for HVSMC due to the generation of enzymatically active thrombin which occurs upon incubation of prothrombin with the cells. Analysis by SDS-PAGE, immunoblotting, and amino acid sequencing revealed that prothrombin incubated with HVSMC undergoes limited proteolysis. Prethrombin 1 was formed through cleavage at R155-S156. Cleavage at R271-T272 generated fragment 1.2 and prethrombin 2 whilst cleavage at R284-T285 yielded truncated prothrombin 2 (prethrombin 2′). However, cleavage at R320-I321 which, during prothrombin activation produces two-chain α-thrombin, was not detectable. Studies on HVSMC-conditioned medium revealed that a similar pattern of prothrombin cleavage occurred by a cell-secreted factor(s). Amidolytic activity analysis indicated that 1–3% catalytically active thrombin-like activity was generated upon incubation of prothrombin with HVSMC-conditioned medium. By treating conditioned medium with various classes of proteinase inhibitors or hirudin, it was determined that prothrombin is cleaved by a cell-derived serine proteinase-like factor(s) at R271-S272 and by α-thrombin at R155-S156 and R284-T285. Antibodies neutralising the activity of either urokinase, tissue plasminogen activator, or factor Xa failed to alter the prothrombin cleaving activity of conditioned medium. This activity which may catalyse an alternative pathway for the generation of thrombin, was eluted from a gel filtration column as a single peak with apparent molecular mass of 30–40 kDa. © 1995 Wiley-Liss, Inc. 相似文献
95.
Jane C. Schneider Hugly Suzanne Chris R. Somerville 《Plant Molecular Biology Reporter》1995,13(1):11-17
Twenty-one mutants ofArabidopsis thaliana were isolated that developed chlorosis or necrosis upon incubation at low temperature (10°C to 15°C). Crosses among mutants
in different phenotypic classes showed that mutants in three of four classes were found in a small number of loci.
This article is reproduced fromWeeds World, vol. 1. For electronic access toWeeds World, see PMBR 12(4):302–303. 相似文献
96.
The crystal structure of glycerol-3-phosphate cytidylyltransferase from B. subtilis (TagD) is about to be solved. Here, we report a testable structure prediction based on the identification by sequence analysis of a superfamily of functionally diverse but structurally similar nucleotide-binding enzymes. We predict that TagD is a member of this family. The most conserved region in this superfamily resembles the ATP-binding HiGH motif of class I aminoacyI-tRNA synthetases. The predicted secondary structure of cytidylyltransferase and its homologues is compatible with the α/β topography of the class I aminoacyl-tRNA synthetases. The hypothesis of similarity of fold is strengthened by sequence-structure alignment and 3D model building using the known structure of tyrosyl tRNA synthetase as template. The proposed 3D model of TagD is plausible both structurally, with a well packed hydrophobic core, and functionally, as the most conserved residues cluster around the putative nucleotide binding site. If correct, the model would imply a very ancient evolutionary link between class I tRNA synthetases and the novel cytidylyltransferase superfamily. © 1995 Wiley-Liss, Inc. 相似文献
97.
Accuracy of predicting protein secondary structure and solvent accessibility from sequence information has been improved significantly by using information contained in multiple sequence alignments as input to a neural 'network system. For the Asilomar meeting, predictions for 13 proteins were generated automatically using the publicly available prediction method PHD. The results confirm the estimate of 72% three-state prediction accuracy. The fairly accurate predictions of secondary structure segments made the tool useful as a starting point for modeling of higher dimensional aspects of protein structure. © 1995 Wiley-Liss, Inc. 相似文献
98.
Defective regulation of the cytosolic Ca2+ activity in parathyroid cells from patients with hyperparathyroidism 总被引:2,自引:0,他引:2
Rolf Larsson Chris Wallfelt Håkan Abrahamsson Erik Gylfe Sverker Ljunghall Jonas Rastad Patrik Rorsman Leif Wide Göran Åkerström 《Bioscience reports》1984,4(11):909-915
The parathyroid hormone (PTH) release and cytosolic Ca2+ activity were determined in normal bovine parathyroid cells and parathyroid cells obtained from patients with hyperparathyroidism (HPT). There was a sigmoid relation between the cytosolic Ca2+ activity and the extracellular calcium concentration between 0.5 and 6.0 mmol/l. The PTH release was inhibited in parallel with the rise in the cytosolic Ca2+ activity. Both the hormone release and the cytosolic Ca2+ activity were lower in cells from human adenomas and hyperplastic glands~ and in comparison with the bovine preparations these ceils had higher set points for the cytosolic Ca2+ activity and PTH release. There was a close correlation between the individual set points for the cytosolic Ca2+ activity and PTH release in a material containing both normal and pathological cells. The results indicate that the abnormal PTH release characteristic of HPT is due to a defective regulation of the cytosolic Ca2+ activity. 相似文献
99.
100.
Peter van der Meijden Chris van der Drift Godfried D. Vogels 《Archives of microbiology》1984,138(4):360-364
The conversion of methanol by cell-free extracts of the acetogenic bacterium Eubacterium limosum was studied. Incubation of mixed cell-free extracts of both E. limosum and Methanobacterium formicicum resulted in methane formation from methanol in the presence of ATP and 2-mercaptoethanesulfonic acid. The separate extracts were not able to perform this reaction. Addition of ferredoxin obtained from Methanosarcina barkeri to the mixed extracts resulted in increased methane formation. The enzyme, responsible for methanol binding in cell-free extract of E. limosum, was inactivated by FAD under N2 and exhibited maximal activity under an atmosphere of H2. This enzyme contains a firmly bound cobalamin which was methylated by methanol in the presence of ATP. It was demethylated in the presence of methylcobalamin: coenzyme M methyltransferase obtained from M. barkeri under concomitant formation of methylated coenzyme M. These properties are similar to those of methanol: 5-hydroxybenzimidazolylcobamide methyltransferase from M. barkeri. It was proposed that methylotrophic acetogens and methylotrophic methanogens use similar enzymes in the first step of methanol conversion.Abbreviations HS-CoM
2-mercaptoethanesulfonic acid
- CH3S-CoM
2-(methylthio)ethanesulfonic acid
- BrES
2-bromoethanesulfonic acid
- TES
N-tris(hydroxymethyl)-methyl-2-aminoethanesulfonic acid
- MT1
methanol: 5-hydroxybenzimidazolylcobamide methyltransferase
- MT2
methylcobalamin
- HS-CoM
methyltransferase
- DMBI
5,6-dimethylbenzimidazole and HBI, 5-hydroxybenzimidazole, are -ligands of corrinoids
- (S-CoM)2
2,2-dithiodiethanesulfonic acid 相似文献