全文获取类型
收费全文 | 145583篇 |
免费 | 8372篇 |
国内免费 | 9446篇 |
出版年
2023年 | 1793篇 |
2022年 | 1972篇 |
2021年 | 3805篇 |
2020年 | 3829篇 |
2019年 | 5759篇 |
2018年 | 4501篇 |
2017年 | 3504篇 |
2016年 | 3854篇 |
2015年 | 5329篇 |
2014年 | 8355篇 |
2013年 | 10892篇 |
2012年 | 6746篇 |
2011年 | 9070篇 |
2010年 | 6775篇 |
2009年 | 7153篇 |
2008年 | 7525篇 |
2007年 | 7731篇 |
2006年 | 7042篇 |
2005年 | 6125篇 |
2004年 | 5286篇 |
2003年 | 4440篇 |
2002年 | 3903篇 |
2001年 | 2889篇 |
2000年 | 2457篇 |
1999年 | 2412篇 |
1998年 | 2286篇 |
1997年 | 1918篇 |
1996年 | 1726篇 |
1995年 | 1886篇 |
1994年 | 1729篇 |
1993年 | 1528篇 |
1992年 | 1552篇 |
1991年 | 1286篇 |
1990年 | 1150篇 |
1989年 | 1051篇 |
1988年 | 1029篇 |
1987年 | 963篇 |
1986年 | 680篇 |
1985年 | 1141篇 |
1984年 | 1604篇 |
1983年 | 1145篇 |
1982年 | 1530篇 |
1981年 | 1104篇 |
1980年 | 1058篇 |
1979年 | 1006篇 |
1978年 | 623篇 |
1977年 | 515篇 |
1976年 | 407篇 |
1975年 | 323篇 |
1973年 | 329篇 |
排序方式: 共有10000条查询结果,搜索用时 62 毫秒
41.
Andrew Leask 《Journal of cell communication and signaling》2010,4(1):71-72
Connective tissue growth factor (CTGF/CCN2) is overexpressed in diabetes. Diabetic rats possess myocardial and cardiomyocyte
hypertrophy. In a recent report, Wang and colleagues (Am J Physiol Cell Physiol. 2009 Jul 22. [Epub ahead of print]) show
that CCN2 directly mediates cardiomyocyte hypertrophy as well as that induced by high glucose and fatty acid. CCN2 acted via
the TrkA receptor. These data are the subject of this commentary, and emphasize that CCN2 may be an excellent target for therapy
in diabetes. 相似文献
42.
We examined whether actin filaments are involved in the cAMP-dependent activation of a high affinity sodium/glucose cotransporter (SGLT1) using epithelial expression systems. The expression of enhanced green fluorescent protein-tagged SGLT1 (EGFP-SGLT1) in Madin-Darby canine kidney (MDCK) cells was revealed by Western blotting and confocal laser microscopy. 8-Br-cAMP, a membrane permeable cAMP analog, enhanced [14C]-α-methyl glucopyranoside ([14C]-AMG) uptake. Both basal and 8-Br-cAMP-elicited [14C]-AMG uptakes were inhibited by N-(2{[3-(4-bromophenyl)-2-propenyl]-amino}-ethyl)-5-isoquinolinesulfonamide (H-89), a protein kinase A inhibitor, and cytochalasin D, an actin filament formation inhibitor. Furthermore, cytochalasin D inhibited the distribution of EGFP-SGLT1 at the apical surface. These results suggest that the EGFP-SGLT1 protein is functionally expressed in the apical membrane of MDCK cells, and is up-regulated by a cAMP-dependent pathway requiring intact actin filaments. 相似文献
43.
The aim of this article is to quantify the drivers for the changes in raw material consumption (domestic material consumption expressed in the form of all materials extracted and used in the production phase) in terms of technology, which refers to the concept of sustainable production; the product structure of final demand, which refers to the concept of sustainable consumption; and the volume of final demand, which is related to economic growth. We also aim to determine to what extent the technological development and a shift in product structure of the final demand compensate for the growth in final consumption volume. Therefore, we apply structural decomposition analysis (SDA) to the change in raw material consumption (RMC) of the Czech Republic between 2000 and 2007. To present the study in a broader context, we also show other material flow indicators for the Czech Republic for 2000 and 2007. Our findings of SDA show that final demand structure has a very limited effect on the change in material flows. The rapid change in final demand volume was not compensated for crude oil, metal ores, construction materials, food crops, and timber. For the material category of non‐iron metal ores, even the change in technology contributes to an increase in material flows. The largest relative increases are reported for non‐iron metal ores (38%) and construction materials (30%). The main changes in material flows related to the Czech Republic are driven by exports and enabled by imports, the main source of these increased material flows. This emphasizes the increasing role of international trade. 相似文献
44.
In order to evaluate the effectiveness and selectivity of various reagents in the solubilization of bacterial membranes, membranes of Micrococcus lysodeikticus were treated with detergents and chaotropic agents. The composition of the extracts so obtained was analyzed by rocket and two-dimensional immunoelectrophoretic techniques. Recovery of succinate-, malate-, and reduced nicotinamide adenine dinucleotide- (NADH) dehydrogenases, ATPase, succinylated lipomannan and cytochromes in the extracts was measured. Treatment with a variety of non-denaturing detergents produced extracts that were generally qualitatively uniform although quantitative differences were observed. The degree of extraction of various components was correlated with the hydrophile-lipophile balance. Several chaotropic agents were also evaluated as reagents for membrane solubilization. These agents were less effective in extraction of bulk protein, but produced extracts enriched in some membrane components. 相似文献
45.
Hanna G. Budayeva Arundhati Sengupta-Ghosh Lilian Phu John G. Moffat Gai Ayalon Donald S. Kirkpatrick 《Molecular & cellular proteomics : MCP》2022,21(4):100221
Muscle-specific receptor tyrosine kinase (MuSK) agonist antibodies were developed 2 decades ago to explore the benefits of receptor activation at the neuromuscular junction. Unlike agrin, the endogenous agonist of MuSK, agonist antibodies function independently of its coreceptor low-density lipoprotein receptor–related protein 4 to delay the onset of muscle denervation in mouse models of ALS. Here, we performed dose–response and time-course experiments on myotubes to systematically compare site-specific phosphorylation downstream of each agonist. Remarkably, both agonists elicited similar intracellular responses at known and newly identified MuSK signaling components. Among these was inducible tyrosine phosphorylation of multiple Rab GTPases that was blocked by MuSK inhibition. Importantly, mutation of this site in Rab10 disrupts association with its effector proteins, molecule interacting with CasL 1/3. Together, these data provide in-depth characterization of MuSK signaling, describe two novel MuSK inhibitors, and expose phosphorylation of Rab GTPases downstream of receptor tyrosine kinase activation in myotubes. 相似文献
46.
47.
A new brain protein is described which forms an insoluble complex with tubulin, with concomitant stoichiometric hydrolysis of GTP. The complex contains a maximum of one tubulin-binding protein (MW 52,500) per two tubulin dimers. The tubulin-binding protein (TBP) does not compete with colchicine, but in the presence of microtubule-associated proteins tubulin appeared less accessible to it. Proteins such as TBP might sequester tubulin and thereby function either to inhibit indiscriminate polymerization, or to promote ordered nucleation by maintaining high local concentrations. 相似文献
48.
D E Bowman 《Biochemical and biophysical research communications》1979,87(1):78-84
The oxidized B chain of insulin was used as a simple model for further consideration of limited proteolysis with low substrate:enzyme ratios. With low B chain:trypsin ratios, the ordinarily slower cleavage rate of the -Lys29-Ala30 bond essentially equaled the cleavage saturation rate of the -Arg22-Gly23 bond. This led to the disappearance of octapeptide which ordinarily forms most rapidly. Heptapeptide and alanine, formed mainly by cleavage of the octapeptide, decreased somewhat at high enzyme relative levels. Trypsin added to B chain formed a single chromatographic peak. 相似文献
49.
J.Kalervo Hiltunen E.Jack Davis 《Biochimica et Biophysica Acta (BBA)/General Subjects》1981,678(1):115-121
The mechanism of depletion of tricarboxylic acid cycle intermediates by isolated rat heart mitochondria was studied using hydroxymalonate (an inhibitor of malic enzymes) and mercaptopicolinate (an inhibitor of phosphoenolpyruvate carboxykinase) as tools. Hydroxymalonate inhibited the respiration rate of isolated mitochondria in state 3 by 40% when 2 mM malate was the only external substrate, but no inhibition was found with 2 mM malate plus 0.5 mM pyruvate as substrates. In the prescence od bicarbonate, arsenite and ATP, propionate was converted to pyruvate and malate at the rates of 14.0 ± 2.9 and 2.8 ± 1.8 nmol/mg protein in 5 min, respectively. Under these conditions, 0.1 mM mercaptopicolinate did not affect this conversion, but 2 mM hydroxymalonate inhibited pyruvate formation completely and resulted in an accumulation of malate up to 13.2 ± 2.9 nmol/mg protein. No accumulation of phosphoenolpyruvate was found under any condition tested. It is concluded that malic enzymes but not phosphoenolpyruvate carboxykinase, are involved in conversion of propionate to pyruvate in isolated rat heart mitochondria. 相似文献
50.
Takashi Arakawa Yoshiaki Kamiya 《Biochemical and biophysical research communications》2010,397(2):345-349
We previously reported the identification of DP-1 isoforms (α and β), which are structurally C-terminus-deleted ones, and revealed the low-level expression of these isoforms. It is known that wild-type DP-1 is degraded by the ubiquitin-proteasome system, but few details are known about the domains concerned with the protein stability/instability for the proteolysis of these DP-1 isoforms. Here we identified the domains responsible for the stability/instability of DP-1. Especially, the DP-1 “Stabilon” domain was a C-terminal acidic motif and was quite important for DP-1 stability. Moreover, we propose that this DP-1 Stabilon may be useful for the stability of other nuclear proteins when fused to them. 相似文献