全文获取类型
收费全文 | 9199篇 |
免费 | 670篇 |
国内免费 | 2篇 |
出版年
2024年 | 4篇 |
2023年 | 46篇 |
2022年 | 115篇 |
2021年 | 220篇 |
2020年 | 132篇 |
2019年 | 172篇 |
2018年 | 226篇 |
2017年 | 188篇 |
2016年 | 312篇 |
2015年 | 500篇 |
2014年 | 582篇 |
2013年 | 682篇 |
2012年 | 819篇 |
2011年 | 841篇 |
2010年 | 550篇 |
2009年 | 425篇 |
2008年 | 555篇 |
2007年 | 559篇 |
2006年 | 484篇 |
2005年 | 499篇 |
2004年 | 421篇 |
2003年 | 399篇 |
2002年 | 346篇 |
2001年 | 80篇 |
2000年 | 56篇 |
1999年 | 81篇 |
1998年 | 90篇 |
1997年 | 64篇 |
1996年 | 54篇 |
1995年 | 56篇 |
1994年 | 45篇 |
1993年 | 41篇 |
1992年 | 24篇 |
1991年 | 26篇 |
1990年 | 27篇 |
1989年 | 17篇 |
1988年 | 13篇 |
1987年 | 11篇 |
1986年 | 13篇 |
1985年 | 9篇 |
1984年 | 11篇 |
1983年 | 13篇 |
1982年 | 15篇 |
1981年 | 11篇 |
1980年 | 5篇 |
1979年 | 5篇 |
1978年 | 7篇 |
1977年 | 5篇 |
1976年 | 5篇 |
1975年 | 3篇 |
排序方式: 共有9871条查询结果,搜索用时 656 毫秒
881.
Becker HM Hirnet D Fecher-Trost C Sültemeyer D Deitmer JW 《The Journal of biological chemistry》2005,280(48):39882-39889
Injection of carbonic anhydrase isoform II (CA) into Xenopus frog oocytes increased the rate of H+ flux via the rat monocarboxylate transporter isoform 1 (MCT1) expressed in the oocytes. MCT1 activity was assessed by changes of intracellular H+ concentration measured by pH-selective microelectrodes during application of lactate. CA-induced augmentation of the rate of H+ flux mediated by MCT1 was not inhibited by ethoxyzolamide (10 microM) and did not depend on the presence of added CO2/HCO3- but was suppressed by injection of an antibody against CA. Deleting the C terminus of the MCT1 greatly reduced its transport rate and removed transport facilitation by CA. Injected CA accelerated the CO2/HCO3(-)-induced acidification severalfold, which was blocked by ethoxyzolamide and was independent of MCT1 expression. Mass spectrometry confirmed activity of CA as injected into the frog oocytes. With pulldown assays we demonstrated a specific binding of CA to MCT1 that was not attributed to the C terminus of MCT1. Our results suggest that CA enhances MCT1 transport activity, independent of its enzymatic reaction center, presumably by binding to MCT1. 相似文献
882.
Piccoli C Ria R Scrima R Cela O D'Aprile A Boffoli D Falzetti F Tabilio A Capitanio N 《The Journal of biological chemistry》2005,280(28):26467-26476
883.
Chigorno V Giannotta C Ottico E Sciannamblo M Mikulak J Prinetti A Sonnino S 《The Journal of biological chemistry》2005,280(4):2668-2675
Human fibroblasts, rat neurons, and murine neuroblastoma cells, cultured in the presence of fetal calf serum, were fed with [1-(3)H]sphingosine to radiolabel sphingolipids. The fate of cell sphingolipids, the release of sphingolipids in the culture medium, the interaction of sphingolipids with the proteins and lipoproteins of fetal calf serum, and the fate of sphingolipids taken up by the cells were investigated. For this latter purpose, the culture medium containing radioactive sphingolipids was delivered to nonlabeled cells. The presence of tritium at position 1 of sphingosine allowed us to follow the extent of sphingolipid catabolism by measuring the production of radioactive phosphatidylethanolamine and proteins by recycling the radioactive ethanolamine formed during sphingosine catabolism and the production of tritiated water. We confirmed that in cells the recycling of sphingosine occurred to a high extent and that only a minor portion of cell sphingolipids was catabolized to the small fragments of ethanolamine and water. Cell sphingolipids were released in the culture medium, where they formed large lipoproteic aggregates at a rate of about 12% per day. Released sphingolipids were taken up by the cells and catabolized to the sphingosine and then to ethanolamine, and recycling of sphingosine was not observed. This suggests that in the presence of fetal calf serum in the culture medium, exogenous sphingolipids directly reach the lysosomes, were they are entirely catabolized. Thus, the trafficking of sphingolipids from cells to the extracellular environment and from this to other cells does not allow the modification of the plasma membrane composition. 相似文献
884.
In neurons, proper distribution of mitochondria in axons and at synapses is critical for neurotransmission, synaptic plasticity, and axonal outgrowth. However, mechanisms underlying mitochondrial trafficking throughout the long neuronal processes have remained elusive. Here, we report that syntabulin plays a critical role in mitochondrial trafficking in neurons. Syntabulin is a peripheral membrane-associated protein that targets to mitochondria through its carboxyl-terminal tail. Using real-time imaging in living cultured neurons, we demonstrate that a significant fraction of syntabulin colocalizes and co-migrates with mitochondria along neuronal processes. Knockdown of syntabulin expression with targeted small interfering RNA or interference with the syntabulin-kinesin-1 heavy chain interaction reduces mitochondrial density within axonal processes by impairing anterograde movement of mitochondria. These findings collectively suggest that syntabulin acts as a linker molecule that is capable of attaching mitochondrial organelles to the microtubule-based motor kinesin-1, and in turn, contributes to anterograde trafficking of mitochondria to neuronal processes. 相似文献
885.
Husseneder C Messenger MT Su NY Grace JK Vargo EL 《Journal of economic entomology》2005,98(5):1421-1434
The Formosan subterranean termite, Coptotermes formosanus Shiraki, is an invasive species in many parts of the world, including the U.S. mainland. The reasons for its invasive success may have to do with the flexible social and spatial organization of colonies. We investigated the population and breeding structure of 14 C. formosanus colonies in Louis Armstrong Park, New Orleans, LA. This population has been the focus of extensive study for many years, providing the opportunity to relate aspects of colony breeding structure to previous findings on colony characteristics such as body weight and number of workers, wood consumption, and intercolony aggression. Eight colonies were headed by a single pair of outbred reproductives (simple families), whereas six colonies were headed by low numbers of multiple kings and/or queens that were likely the neotenic descendants of the original colony (extended families). Within the foraging area of one large extended family colony, we found genetic differentiation among different collection sites, suggesting the presence of separate reproductive centers. No significant difference between simple family colonies and extended family colonies was found in worker body weight, soldier body weight, foraging area, population size, or wood consumption. However, level of inbreeding within colonies was negatively correlated with worker body weight and positively correlated with wood consumption. Also, genetic distance between colonies was positively correlated with aggression levels, suggesting a genetic basis to nestmate discrimination cues in this termite population. No obvious trait associated with colony reproductive structure was found that could account for the invasion success of this species. 相似文献
886.
Three Formosan subterranean termite, Coptotermes formosanus Shiraki (Isoptera: Rhinotermitidae), colonies located inside the 12.75-ha Louis Armstrong Park, New Orleans, were selected for elimination by using the chitin synthesis inhibitor hexaflumuron. Once eliminated, each vacated foraging territory was monitored for reinvasion by neighboring C. formosanus colonies, Reticulitermnes flavipes (Kollar) (Isoptera: Rhinotermitidae) colonies, or both. Each selected colony was eliminated in approximately 3 mo by using baits containing hexaflumuron. Overall activity of each untreated colony in the park remained unchanged during the same period. New C. formosanus and R. flavipes activity was detected in two of the three vacated territories, and in both areas, within days of selected colony elimination. The third vacated territory was completely reoccupied by a new C. formosanus colony approximately 7 mo later. Mark-recapture studies and DNA fingerprinting confirmed the distinctness of the reinvaders from eliminated and neighboring colonies. 相似文献
887.
Weier D Müller C Gaspers C Frentzen M 《Biochemical and biophysical research communications》2005,334(4):1127-1134
As phylogenetic ancestors of plant chloroplasts cyanobacteria resemble plastids with respect to lipid and fatty acid composition. These membrane lipids show the typical prokaryotic fatty acid pattern in which the sn-2 position is exclusively esterified by C(16) acyl groups. In the course of de novo glycerolipid biosynthesis this prokaryotic fatty acid pattern is established by the sequential acylation of glycerol-3-phosphate with acyl-ACPs by the activity of different acyltransferases. In silico approaches allowed the identification of putative Synechocystis acyltransferases involved in glycerolipid metabolism. Functional expression studies in Escherichia coli showed that sll1848 codes for a lysophosphatidic acid acyltransferase with a high specificity for 16:0-ACP, whereas slr2060 encodes a lysophospholipid acyltransferase, with a broad acyl-ACP specificity but a strong preference for lysophosphatidyglycerol especially its sn-2 acyl isomer as acyl-acceptor. The generation and analysis of the corresponding Synechocystis knockout mutants revealed that lysophosphatidic acid acyltransferase unlike the lysophospholipid acyltransferase is essential for the vital functions of the cells. 相似文献
888.
889.
Roberts SJ Stewart AJ Schmid R Blindauer CA Bond SR Sadler PJ Farquharson C 《Biochimica et biophysica acta》2005,1752(1):73-82
PHOSPHO1, a phosphoethanolamine/phosphocholine phosphatase, is upregulated in mineralising cells and is thought to be involved in the generation of inorganic phosphate for bone mineralisation. PHOSPHO2 is a putative phosphatase sharing 42% sequence identity with PHOSPHO1. Both proteins contain three catalytic motifs, conserved within the haloacid dehalogenase superfamily. Mutation of Asp32 and Asp203, key residues within two motifs, abolish PHOSPHO1 activity and confirm it as a member of this superfamily. We also show that Asp43 and Asp123, residues that line the substrate-binding site in our PHOSPHO1 model, are important for substrate hydrolysis. Further comparative modelling reveals that the active sites of PHOSPHO1 and PHOSPHO2 are very similar, but surprisingly, recombinant PHOSPHO2 hydrolyses phosphoethanolamine and phosphocholine relatively poorly. Instead, PHOSPHO2 shows high specific activity toward pyridoxal-5-phosphate (V(max) of 633 nmol min(-1) mg(-1) and K(m) of 45.5 microM). Models of PHOSPHO2 and PHOSPHO1 suggest subtle differences in the charge distributions around the putative substrate entry site and in the location of potential H-bond donors. 相似文献
890.
Goi G Massaccesi L Burlina AP Baquero Herrera CJ Lombardo A Tettamanti G Burlina AB 《Biochimica et biophysica acta》2005,1741(3):300-306
OBJECTIVE: Fabry disease results from a deficiency in the activity of alpha-d-galactosidase A and subsequent accumulation of neutral glycosphingolipids in lysosomes. This study investigated whether lysosomal enzymes can indicate biochemical changes in the lysosomal apparatus induced by enzyme replacement therapy (ERT). DESIGN AND METHODS: Eight patients were monitored by clinical and biochemical tests and several lysosomal glycohydrolases were measured in plasma and leucocytes. RESULTS: Before starting ERT, beta-d-glucuronidase in leukocytes was markedly increased. After 1 month of therapy, enzyme levels dropped in all patients. In the patients who regularly followed the therapy, the enzyme levels remained stable for the next 20 months. In one patient who interrupted therapy for 2 months, the enzyme levels rose again. CONCLUSIONS: Lysosomal enzymes can be useful for monitoring biochemical changes in patients with Fabry disease receiving ERT. Though these findings refer to only a small number of patients, the correlation between beta-d-glucuronidase levels and ERT is interesting and might serve as a basis for further studies to define the potential of this enzyme in monitoring the effects of ERT in lysosomal storage disorders. 相似文献