全文获取类型
收费全文 | 21040篇 |
免费 | 2136篇 |
国内免费 | 226篇 |
专业分类
23402篇 |
出版年
2023年 | 81篇 |
2022年 | 235篇 |
2021年 | 388篇 |
2020年 | 242篇 |
2019年 | 355篇 |
2018年 | 472篇 |
2017年 | 360篇 |
2016年 | 617篇 |
2015年 | 1004篇 |
2014年 | 1117篇 |
2013年 | 1265篇 |
2012年 | 1559篇 |
2011年 | 1482篇 |
2010年 | 1033篇 |
2009年 | 832篇 |
2008年 | 1143篇 |
2007年 | 1052篇 |
2006年 | 978篇 |
2005年 | 912篇 |
2004年 | 901篇 |
2003年 | 763篇 |
2002年 | 736篇 |
2001年 | 458篇 |
2000年 | 406篇 |
1999年 | 331篇 |
1998年 | 202篇 |
1997年 | 174篇 |
1996年 | 138篇 |
1995年 | 126篇 |
1994年 | 150篇 |
1993年 | 129篇 |
1992年 | 228篇 |
1991年 | 240篇 |
1990年 | 204篇 |
1989年 | 231篇 |
1988年 | 186篇 |
1987年 | 189篇 |
1986年 | 187篇 |
1985年 | 163篇 |
1984年 | 143篇 |
1983年 | 117篇 |
1982年 | 119篇 |
1981年 | 119篇 |
1980年 | 105篇 |
1979年 | 124篇 |
1978年 | 128篇 |
1976年 | 99篇 |
1975年 | 106篇 |
1974年 | 108篇 |
1973年 | 99篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
61.
The constitution and properties of phosphorylated and unphosphorylated C-terminal fragments of progastrin from dog and ferret antrum 总被引:1,自引:0,他引:1
Antibodies to the extreme C-terminal tryptic (nona-) peptide fragment of porcine progastrin have been used in radioimmunoassay to identify progastrin fragments in dog, ferret and pig antral mucosa extracts and to monitor their purification. In addition to previously characterised phosphorylated and unphosphorylated C-terminal tryptic peptides of porcine progastrin a minor form corresponding to the C-terminal octapeptide (i.e. des-Ser C-terminal nonapeptide) was isolated and characterised. The latter form together with phosphorylated and unphosphorylated forms of the nonapeptides were also isolated and chemically characterised from dog antrum, and the unphosphorylated nonapeptide was characterised from ferret antrum. The primary amino acid sequences of the dog, ferret and pig nonapeptides were identical. In ferret the unphosphorylated nonapeptide predominated, and in dog the phosphorylated form predominated; in pig both forms of the nonapeptide were well represented. Intact progastrin was identified in gel filtration eluates of extracts of all 3 species, but occurred only in relatively low concentrations. The nonapeptides did not stimulate acid secretion in the conscious gastric fistula rat and they did not modify the acid response to G17. Phosphorylation of progastrin-derived peptides is evidently well conserved across a range of species even though there appear to be differences in the relative proportions of phosphorylated and unphosphorylated forms. 相似文献
62.
A C-terminal domain of GAP is sufficient to stimulate ras p21 GTPase activity. 总被引:41,自引:8,他引:33 下载免费PDF全文
M S Marshall W S Hill A S Ng U S Vogel M D Schaber E M Scolnick R A Dixon I S Sigal J B Gibbs 《The EMBO journal》1989,8(4):1105-1110
The cDNA for bovine ras p21 GTPase activating protein (GAP) has been cloned and the 1044 amino acid polypeptide encoded by the clone has been shown to bind the GTP complexes of both normal and oncogenic Harvey (Ha) ras p21. To identify the regions of GAP critical for the catalytic stimulation of ras p21 GTPase activity, a series of truncated forms of GAP protein were expressed in Escherichia coli. The C-terminal 343 amino acids of GAP (residues 702-1044) were observed to bind Ha ras p21-GTP and stimulate Ha ras p21 GTPase activity with the same efficiency (kcat/KM congruent to 1 x 10(6) M-1 s-1 at 24 degrees C) as GAP purified from bovine brain or full-length GAP expressed in E. coli. Deletion of the final 61 amino acid residues of GAP (residues 986-1044) rendered the protein insoluble upon expression in E. coli. These results define a distinct catalytic domain at the C terminus of GAP. In addition, GAP contains amino acid similarity with the B and C box domains conserved among phospholipase C-II, the crk oncogene product, and the non-receptor tyrosine kinase oncogene products. This homologous region is located in the N-terminal half of GAP outside of the catalytic domain that stimulates ras p21 GTPase activity and may constitute a distinct structural or functional domain within the GAP protein. 相似文献
63.
Dual translational initiation sites control function of the lambda S gene. 总被引:17,自引:3,他引:14 下载免费PDF全文
Lysis gene S of phage lambda has a 107 codon reading frame beginning with the codons Met1-Lys2-Met3. Genetic data have suggested that translational initiation occurs at both Met1 and Met3, generating two polypeptides, S107 and S105 respectively. We have proposed a model in which the proper scheduling of lysis depends on the partition of translational initiations between the two start codons. Here, using in vitro methods, we show that two stem-loop structures, one immediately upstream of the reading frame and a second approximately 10 codons within the gene, control the partitioning event. Utilizing primer-extension inhibition or 'toeprinting', we show that the two S start codons are served by two adjacent Shine-Dalgarno sequences. Moreover, the timing of lysis supported by the wild-type and a number of mutant alleles in vivo can be correlated with the ratio of ternary complex formation over Met1 and Met3 in vitro. Thus the regulation of the S gene is unique in that the products of two adjacent in-frame initiation events have opposing function. 相似文献
64.
65.
T J Gana B R MacPherson D Ng J Koo 《Canadian journal of physiology and pharmacology》1989,67(4):353-358
We studied the dose response of ionic fluxes in canine chambered gastric segment mucosa to increasing doses of topical misoprostol (0.1, 1, 10, 100, and 1000 micrograms). The fluxes were also correlated with the simultaneous changes in focal gastric mucosal blood flow measured by laser-Doppler flowmetry. After misoprostol administration, there was a dose-dependent increase in focal gastric mucosal blood flow (Emax = 8.23 +/- 3.25 V at 10 micrograms; ED50 = 1.05 micrograms), pH, and the outputs of ions (Na+, K+, Cl-, and HCO3-) and fluid (Emax for pH and fluxes greater than or equal to 1000 micrograms). ED50 values for these outputs ranged from 215.40 to 340 micrograms (mean +/- SE = 279.08 +/- 24.27 micrograms). H+ output showed a dose-dependent decrease to zero at the 10-micrograms dose, the dose at and after which net HCO3- secretion became obvious. The slopes of the dose-response curves for the fluxes of fluid, Na+, K+, Cl-, and HCO3- were significantly different (p less than 0.01) from the slope of the curve for mucosal blood flow changes. There were no correlations between the changes in these fluxes and blood flow changes. Na+ and Cl- were the predominant cation (98.84%) and anion (98.19%), respectively, in the misoprostol-induced secretion. Misoprostol stimulates a composite alkaline gastric nonparietal secretion, predominantly Na+ and Cl-, but also containing K+ and HCO3-. Our results suggest different mechanisms for the effects on nonparietal secretion and focal gastric mucosal blood flow.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
66.
A cdc2-3w weel-50 double mutant of fission yeast displays a temperature-sensitive lethal phenotype that is associated with gross abnormalities of chromosome segregation and has been termed mitotic catastrophe. In order to identify new genetic elements that might interact with the cdc2 protein kinase in the regulation of mitosis, we have isolated revertants of the lethal double mutant. The suppressor mutations define six mcs genes (mcs: mitotic catastrophe suppressor) that are not allelic to any of the following mitotic control genes: cdc2, wee 1, cdc13, cdc25, suc1 or nim1. Each mcs mutation is recessive with respect to wild-type in its ability to suppress mitotic catastrophe. None confer a lethal phenotype as a single mutant but few of the mutants are expected to be nulls. A diverse range of genetic interactions between the mcs mutants and other mitotic regulators were uncovered, including the following examples. First, mcs2 cdc2w or mcs6 cdc2w double mutants display a cell cycle defect dependent on the specific wee allele of cdc2. Second, both mcs1 cdc25-22 or mcs4 cdc25-22 double mutants are nonconditionally lethal, even at a temperature normally permissive for cdc25-22. Finally, the characteristic suppression of the cdc25 phenotype by a loss-of-function wee1 mutation is reversed in a mcs3 mutant background. The mcs genes define new mitotic elements that might be activators or substrates of the cdc2 protein kinase. 相似文献
67.
A lethally malformed neonate with mosaic tetrasomy 12p is presented. This is the third reported case of mosaic tetrasomy 12p to have died in the neonatal period. These three babies have shown a consistent phenotype characterized by dysmorphic facies and large diaphragmatic hernia. Mosaic tetrasomy 12p is usually not detectable from lymphocyte investigation, indicating that chromosome studies from cultured fibroblasts should be undertaken in neonates with multiple malformations which include a diaphragmatic defect. 相似文献
68.
A J Ping A E Reeve D J Law M R Young M Boehnke A P Feinberg 《American journal of human genetics》1989,44(5):720-723
Beckwith-Wiedemann syndrome (BWS), characterized by multiorgan developmental abnormalities and predisposition to cancer, usually occurs sporadically, but small apparently dominant pedigrees have been described. Since rare patients show varying karyotypic abnormalities on the short arm of chromosome 11, it has been suggested that BWS may be related to the Wilms tumor gene on 11p13 or, alternatively, to growth factor genes on 11p15. We performed genetic linkage analysis on two BWS kindreds, using RFLPs for loci on 11p. BWS was linked to the insulin gene (11p15.5), with an overall maximum lod score of 3.60 (recombination fraction = .00). Linkage to D11S16 (11p13) could be excluded for recombination fractions less than or equal to .03. These results suggest that BWS defines a tumor-predisposition gene on 11p15. 相似文献
69.
Differential susceptibility of type III erythrocytes of paroxysmal nocturnal hemoglobinuria to lysis mediated by complement and perforin 总被引:1,自引:0,他引:1
S Jiang P M Persechini W F Rosse B Perussia J D Young 《Biochemical and biophysical research communications》1989,162(1):316-325
Previous reports have suggested that a 65 kDa membrane protein, termed homologous restriction factor (HRF), in addition to protecting erythrocytes (E) against lysis by homologous complement (C), may also be involved in protecting cytolytic lymphocytes against lysis mediated by a pore-forming protein (PFP/perforin), one of their own lytic mediators. Here, we used HRF-deficient type III E of patients with paroxysmal nocturnal hemoglobinuria (PNH) to study their susceptibility to lysis mediated by homologous C and perforin, and compared it with lysis of HRF-bearing control or PNH type I E. We show that type III E of PNH patients are indeed more susceptible to lysis mediated by homologous C than control or type I E, but they are as susceptible to perforin-mediated lysis as type I E. In addition, all human E (type I or III) tested here are equally susceptible to lysis mediated by either human (homologous) or murine (heterologous) perforin. By immunoblot analysis, we confirm that type III E, in contrast to type I E, were deficient in the 65 kDa HRF. These results support the notion that homologous species restriction is seen in the C- but not in the lymphocyte perforin-system and argue against an active participation of HRF in protecting cells from perforin-mediated lysis. 相似文献
70.
The antiproliferative effect of 10(-6) M antiestrogens in an estrogen receptor-negative lymphoid cell line (K36) was enhanced in lipoprotein-poor growth medium. The enhancement was not due to increased bioavailability because cellular uptake of [3H]tamoxifen was not increased and the lipoprotein fraction of serum had negligible [3H]tamoxifen-binding capacity. Cholesterol and lipoproteins, but not mevalonate, reversed the cytostatic effect of antiestrogens. Reversal by cholesterol was dose-related (10(-7) M to 10(-5) M), while that by lipoproteins could also be demonstrated in medium undepleted of lipoproteins. The cytostatic efficacy of a series of ten compounds correlated well with their relative binding affinities for solubilized antiestrogen-binding sites from K36 cells when log IC50 values (concentration required to reduce [3H]thymidine incorporation by 50%) were plotted against log RBA50 values (concentration required to reduce [3H]tamoxifen binding by 50%) (correlation coefficient 0.94). Transmission electron microscopy of antiestrogen-treated cells showed evidence of disordered cytokinesis which was partially reversed by cholesterol. These observations implicate the antiestrogen-binding protein in the antiproliferative effect of antiestrogens in nonestrogen target cells. 相似文献