全文获取类型
收费全文 | 11806篇 |
免费 | 1331篇 |
国内免费 | 3篇 |
出版年
2022年 | 70篇 |
2021年 | 134篇 |
2020年 | 142篇 |
2019年 | 221篇 |
2018年 | 240篇 |
2017年 | 257篇 |
2016年 | 324篇 |
2015年 | 526篇 |
2014年 | 531篇 |
2013年 | 723篇 |
2012年 | 708篇 |
2011年 | 635篇 |
2010年 | 532篇 |
2009年 | 465篇 |
2008年 | 565篇 |
2007年 | 581篇 |
2006年 | 568篇 |
2005年 | 614篇 |
2004年 | 580篇 |
2003年 | 628篇 |
2002年 | 634篇 |
2001年 | 121篇 |
2000年 | 102篇 |
1999年 | 156篇 |
1998年 | 199篇 |
1997年 | 142篇 |
1996年 | 142篇 |
1995年 | 142篇 |
1994年 | 123篇 |
1993年 | 90篇 |
1992年 | 128篇 |
1991年 | 100篇 |
1990年 | 91篇 |
1989年 | 93篇 |
1988年 | 72篇 |
1987年 | 87篇 |
1986年 | 78篇 |
1985年 | 95篇 |
1984年 | 102篇 |
1983年 | 83篇 |
1982年 | 107篇 |
1981年 | 119篇 |
1980年 | 90篇 |
1979年 | 92篇 |
1978年 | 90篇 |
1977年 | 80篇 |
1976年 | 83篇 |
1975年 | 53篇 |
1974年 | 73篇 |
1973年 | 66篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
201.
202.
Jesús Mateo Enrique Castro Jean Zwiller Dominique Aunis M. T. Miras-Portugal 《Journal of neurochemistry》1995,64(1):77-84
Abstract: We investigated the effect of the adenosine receptor agonist 5'-( N -ethylcarboxamido)adenosine (NECA) in catecholamine secretion from adrenal chromaffin cells that exhibit only the A2b subtype adenosine receptor. NECA reduced catecholamine release evoked by the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP) in a time-dependent manner. Inhibition reached 25% after 30–40-min exposure to NECA. This effect on DMPP-evoked catecholamine secretion was mirrored by a similar (27.7 ± 3.3%), slowly developing inhibition of [Ca2+ ]i transients induced by DMPP that peaked at 30-min preincubation with NECA. The capacity of the chromaffin cells to buffer Ca2+ load was not affected by the treatment with NECA. Short-term treatment with NECA failed both to modify [Ca2+ ]i levels and to increase endogenous diacylglycerol production, showing that NECA does not activate the intracellular Ca2+ /protein kinase C signaling pathway. The inhibitory effects of NECA were accompanied by a 30% increase of protein phosphatase activity in chromaffin cell cytosol. We suggest that dephosphorylation of a protein involved in DMPP-evoked Ca2+ influx pathway (e.g., L-type Ca2+ channels) could be the mechanism of the inhibitory action of adenosine receptor stimulation on catecholamine secretion from adrenal chromaffin cells. 相似文献
203.
Stream-dwelling insects and extremely low frequency electromagnetic fields: a ten-year study 总被引:1,自引:0,他引:1
Changes in the structure of benthic insect communities at an experimental site and at a reference site in the Ford River, Michigan were monitored over a 10-year period to determine whether extremely low frequency electromagnetic fields (ELF) affected those communities. Five of 10 biotic parameters monitored are presented: taxon evenness (J), richness (S), numerical dominance of chironomids, and total insect mass. Data were separated into three seasons because coefficient of variation values were lower in the summer than in the spring and fall. Two-way ANOVA tests for the biotic variables were often significantly different between sites and among years, but the interaction terms were less frequently significant. Biotic parameters were regressed against stream discharge, water temperatures, years, and ELF cumulative ground field exposures. At the experimental site, discharge accounted for more variation than did water temperature or years for all biotic parameters except chironomid numerical dominance in the fall. Intervention analyses, using the B.A.C.I parametric or the R.I.A non-parametric showed significant differences in three of 15 cases; namely, for the highly varying chironomid numerical dominance values in the spring and fall and for the low varying total insect mass values in the summer. For those tests, the Before Impact period spanned April 1984 through May 1986. The After Impact period (full ELF power) spanned June 1989 through August 1993. Trend analysis for total insect mass at the experimental site in the summer showed discharge to be more important than water temperatures or ELF ground field exposures. Natural physical factors appear to be more important than the anthropogenic ELF fields in accounting for seasonal and yearly changes in the community. 相似文献
204.
High level biosynthesis and secretion of the thermostable hybrid (1-3,1-4)--glucanase H(A16-M) has been achieved inSaccharomyces cerevisiae by means of the yeast vacuolar endoprotease B promoter (PRB1p) and theBacillus macerans (1-3,1-4)--glucanase signal peptide. The N-glycans present on the yeast-secreted H(A16-M), denoted H(A16-M)-Y, were released by endoglycosidase H, and identified by proton NMR spectroscopy to be a homologous series of Man8-13GlcNAc2, although only traces of Man9GlcNAc2 were found. Therefore, processing of N-glycans on H(A16-M)-Y is similar to that on homologous proteins. Most of the N-glycans (88%) were neutral while the remainder were charged due to phosphorylation. Site-directed mutagenesis of Asn to Gln in two of the N-glycosylation sequons, and subsequent analysis of the N-glycans on the yeast-secreted proteins together with analysis of the N-glycans from the individual sites of H(A16-M)-Y suggest the presence of steric hindrance to glycan modification by the glycans themselves. H(A16-M)-Y produced under control of either the yeast protease B or the yeast 3-phosphoglycerate kinase promoter, each in two differentSaccharomyces strains revealed a dependence of N-glycan profile on both strain and culture conditions. The extent of O-glycosylation was found to be nine mannose units per H(A16-M)-Y molecule. An attempt to identify the linkage-sites for the O-glycans by amino acid sequencing failed, suggesting non-stoichiometric or heterogeneous O-glycosylation. The possible modes in which N-glycans might contribute to resistance of H(A16-M)-Y to irreversible thermal denaturation are discussed with respect to structural information available for H(A16-M)-Y.
Abbreviations: AMY,B. amyloliquefaciens (1-3,1-4)--glucanse; MAC,B. macerans (1-3,1-4)--glucanase H(A16-M), H(A36-M), H(A78-M),H(A107-M) and H(A152-M), hybrid (1-3,1-4)--glucanases containing 16, 36, 78, 107 and 152 N-terminal amino acids, respectively, derived from AMY with the remaining amino acids derived from MAC; similar enzyme abbreviations followed by Y, e.g. H(A16-M)-Y, denote the enzymes secreted from yeast cells; PCR, polymerase chain reaction; PGKp, yeast 3-phosphoglycerate kinase promoter; PRB1p, yeast protease B promoter; LB, Luria-Bertani medium; SC, minimal medium; CNBr, cyanogen bromide; Endo Hf, endoglycosidase H fusion protein; PNGase F, peptide:N-glycosidase F; HPAEC; high pH anion exchange chromatography; HVE, high voltage paper electrophoresis; CPY, yeast carboxypeptidase Y. 相似文献
205.
Sabine Castano Bernard Desbat Isabelle Cornut Philippe Méléard Jean Dufourcq 《Letters in Peptide Science》1997,4(4-6):195-200
De novo designed extremely simplified amphipathic basicLeuiLysj (i = 2j) peptides of 8, 9 and 15residues were synthesized to clarify the mechanism of action of naturalcytotoxic and hemolytic small proteins or peptides. They proved to havestrong hemolytic activity towards human erythrocytes which increases withpeptide length. These peptides are highly surface active and form stablepeptidic films at the air/water interface. The sensitive and efficient FTIRmodulated polarization technique (PMIRRAS) allows one to obtain in situstructural and orientational information about the peptides at theinterface. A transition of secondary structure is observed: the shorterpeptides (8 and 9 residues) adopt -sheet structures while the longerone (15 residues) is folded into an -helix. In both cases, the peptideslie with the axis parallel to the interface. Their insertion into adimyristoylphosphatidylcholine monolayer can be followed from the increasein the surface and/or pressure of the films. In the mixed films, thepeptides adopt the same structure and orientation as observed at theair/water interface. Therefore, among the same series of peptides, atransition from -sheet to -helix occurs when the length increases(roughly >10 aa), but despite this drastic change both types ofstructures result in strongly hemolytic peptides. 相似文献
206.
Positive role of macaque cytotoxic T lymphocytes during SIV infection: decrease of cellular viremia and increase of asymptomatic clinical period 总被引:1,自引:0,他引:1
207.
Florine Cavelier Christine Enjalbal Jérome Santolini Francis Haraux Claude Sigalat Jean Verducci François André 《Letters in Peptide Science》1997,4(4-6):283-288
Tentoxin[cyclo-(MeAla1-Leu2-MePhe3-Gly4] is a metabolite isolated from a phytopathogenic fungusAlternaria alternata, which induces chlorosis of many plants. This potentialnatural herbicide binds specifically to the soluble part CF1of the chloroplastic coupling factor, which is a proton ATP-synthase. Theeffect of the toxin is concentration dependent: at low concentration it is apowerful inhibitor, while at higher concentration, it stimulates the enzyme.We synthesized tentoxin and we designed new analogues in order to vary thehydrophobicity on the side chain and to study the structure activityrelationships. Comparative activities suggest that it is possible toseparate inhibitory and activating effects using tentoxin analogues, showingsome evidence for the existence of two binding sites with different affinityconstant. 相似文献
208.
209.
T. N. Ferraro G. T. Golden G. G. Smith N. J. Schork P. St. Jean C. Ballas H. Choi W. H. Berrettini 《Mammalian genome》1997,8(3):200-208
Mature DBA/2J (D2) mice are very sensitive to seizures induced by various chemical and physical stimuli, whereas C57BL/6J
(B6) mice are relatively seizure resistant. We have conducted a genome-wide search for quantitative trait loci (QTLs) influencing
the differential sensitivity of these strains to kainic acid (KA)-induced seizures by studying an F2 intercross population. Parental, F1, and F2 mice (8–10 weeks of age) were injected subcutaneously with 25 mg/kg of KA and observed for 3 h. Latencies to focal and generalized
seizures and status epilepticus were recorded and used to calculate an overall seizure score. Results of seizure testing indicated
that the difference in susceptibility to KA-induced seizures between D2 and B6 mice is a polygenic phenomenon with at least
65% of the variance due to genetic factors. First-pass genome screening (10-cM marker intervals) in F2 progeny (n = 257) documented a QTL of moderate effect on Chromosome (Chr) 1 with a peak LOD score of 5.5 (17% of genetic
variance explained) localized between D1Mit30 and D1Mit16. Provisional QTLs of small effect were detected on Chr 11 (D11Mit224–D11Mit14), 15 (D15Mit6–D15Mit46) and 18 (D18Mit9–D18Mit144). Multiple locus models generally confirmed the Mapmaker/QTL results and also provided evidence for another QTL on Chr 4
(D4Mit9). Multilocus analysis of seizure severity suggested that additional loci on Chrs 5 (D5Mit11), 7 (D7Mit66), and 15 (D15Nds2) might also contribute to KA-induced seizure response. Overall, our results document a complex genetic determinism for KA-induced
seizures in these mouse strains with contributions from as many as eight QTLs.
Received: 16 April 1996 / Accepted: 21 October 1996 相似文献
210.
Inês A. C. Pereira Jean LeGall António V. Xavier M. Teixeira 《Journal of biological inorganic chemistry》1997,2(1):23-31
The high-molecular-mass cytochromes c (Hmcs) from the sulfate-reducing bacteria Desulfovibrio gigas and Desulfovibrio vulgaris (Hildenborough) were found to be strongly bound to the cytoplasmic membrane. After detergent solubilization they were shown to be water soluble and to be similar to those previously isolated from the soluble fractions in terms of N-terminal sequence, molecular mass, UV-visible and EPR spectroscopies. In D. gigas, higher amounts of Hmc can be obtained from the membranes than from the soluble fraction. This enabled further characterization of both cytochromes. The apparent heme reduction potentials of both Hmcs, determined at pH 7.5 through visible and EPR redox titrations, span a large range of redox potentials, approximately between 0 and –280?mV, and can be roughly divided into three groups: four to five hemes have E 0s of –30?mV to –100?mV, three to four hemes have E 0s around –170?mV, and seven to eight hemes have a lower E 0 of –250 to –280?mV. Several of these redox potentials are strongly pH dependent. Mössbauer studies of oxidized and reduced D. vulgaris Hmc show that this protein contains two high-spin hemes in both oxidation states. The rate of reduction of both Hmcs with the periplasmic hydrogenases from the corresponding organisms is extremely slow. 相似文献