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991.
Murata Y Tsuruzoe K Kawashima J Furukawa N Kondo T Motoshima H Igata M Taketa K Sasaki K Kishikawa H Kahn CR Toyonaga T Araki E 《Biochemical and biophysical research communications》2007,364(2):301-307
Insulin receptor substrate-1 (IRS-1) is the major substrate of both the insulin receptor and the IGF-1 receptor. In this study, we created IRS-1 transgenic (IRS-1-Tg) mice which express human IRS-1 cDNA under control of the mouse IRS-1 gene promoter. In the IRS-1-Tg mice, IRS-1 mRNA expression was significantly increased in almost all tissues, but its protein expression was increased in very limited tissues (epididymal fat and skeletal muscle). IRS-1-Tg mice showed glucose intolerance and significantly enlarged epididymal fat mass, as well as elevated serum TNF-α concentrations. Importantly insulin signaling was significantly attenuated in the liver of IRS-1-Tg mice, which may contribute to the glucose intolerance. Our results suggest that excess IRS-1 expression may not provide a beneficial impact on glucose homeostasis in vivo. 相似文献
992.
Michael J. W. Stokesbury Ronan Cosgrove Andre Boustany Daragh Browne Steven L. H. Teo Ronald K. O’Dor Barbara A. Block 《Hydrobiologia》2007,582(1):91-97
Pop-up satellite archival tags were attached to six Atlantic bluefin tuna (Thunnus thynnus) off the west coast of Ireland in autumn 2003 and 2004. The satellite tags measured pressure, ambient temperature and light
for the term of deployment. Radio pop-up satellite endpoint positions, light and sea surface temperature estimations of geolocation
indicate that two fish tagged minutes apart off the coast of County Donegal, migrated to the eastern and western Atlantic
Ocean over the following 8 months. The two fish were 5218 km apart at the termination of the experiment. After tagging in
September and popping up the following March and April, one fish had traveled to the western Atlantic while the other was
located in the waters off the southwest coast of Portugal. A third fish tagged off the coast of County Donegal in October
2004 moved into the Mediterranean Sea and was caught by a fishing vessel southeast of Malta on 11 June 2005. The results link
bluefin tuna feeding on European foraging grounds with known eastern breeding regions and western Atlantic waters. 相似文献
993.
Complexes of Zn(II), Cu(II) and Co(II) with either N-(2-methylpyridyl)-3-thienyl-alkyl-carboxamide or N-(2-pyridyl)-3-thienylalkyl-carboxamide groups have been prepared and characterized. Crystal structures of ten new complexes are reported and discussed. N-(2-Methylpyridyl)-3-thienyl-alkyl-carboxamide exhibits both uni- and bidentate behavior. With all ligands, bidentate complexation is through the carbonyl oxygen and pyridine nitrogen atoms (O, N) and the amide nitrogen atom remains protonated. The electrochemical behavior and the infrared spectra of selected complexes are discussed. 相似文献
994.
Cees S. Roselaar Ronald Sluys Mansour Aliabadian Peter G. M. Mekenkamp 《Journal of Ornithology》2007,148(3):271-280
A database was created of digitized equal area distribution maps of 3,036 phylogenetic species of Palearctic songbirds. Biogeographic
patterns are reported for two data sets: (1) including all passeriform bird species reported as breeding within the boundaries
of our study map, (2) passeriform species restricted in their distribution to our study region, thus excluding the partly
extra-limital taxa. With respect to the data set excluding partly extra-limital taxa, the average range size is 238 grid cells
(grid cell area: 4,062 km2). Analysis of the geographic distribution of species richness for the full data set showed several hotspot regions, mostly
located in mountainous areas. The index of range-size rarity identified similar hotspot regions as that for species richness,
albeit that the range-size rarity de-emphasized the central Siberian hotspot. Range-size rarity hotspots that are not evident
on the measure of species richness concern a great number of islands. Much more prominent on the index of range-size rarity
are the Atlas Mountains of northern Africa, the Jabal al Akhdar region in NE Libya, and the eastern border of the Mediterranean.
Restricting the analysis of geographic variation to the 25% of the species with smallest ranges resulted in a greatly simplified
pattern of hotspots.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
995.
Phosphopantetheine adenylyltransferase from Escherichia coli: investigation of the kinetic mechanism and role in regulation of coenzyme A biosynthesis 下载免费PDF全文
Miller JR Ohren J Sarver RW Mueller WT de Dreu P Case H Thanabal V 《Journal of bacteriology》2007,189(22):8196-8205
Phosphopantetheine adenylyltransferase (PPAT) from Escherichia coli is an essential hexameric enzyme that catalyzes the penultimate step in coenzyme A (CoA) biosynthesis and is a target for antibacterial drug discovery. The enzyme utilizes Mg-ATP and phosphopantetheine (PhP) to generate dephospho-CoA (dPCoA) and pyrophosphate. When overexpressed in E. coli, PPAT copurifies with tightly bound CoA, suggesting a feedback inhibitory role for this cofactor. Using an enzyme-coupled assay for the forward-direction reaction (dPCoA-generating) and isothermal titration calorimetry, we investigated the steady-state kinetics and ligand binding properties of PPAT. All substrates and products bind the free enzyme, and product inhibition studies are consistent with a random bi-bi kinetic mechanism. CoA inhibits PPAT and is competitive with ATP, PhP, and dPCoA. Previously published structures of PPAT crystallized at pH 5.0 show half-the-sites reactivity for PhP and dPCoA and full occupancy by ATP and CoA. Ligand-binding studies at pH 8.0 show that ATP, PhP, dPCoA, and CoA occupy all six monomers of the PPAT hexamer, although CoA exhibits two thermodynamically distinct binding modes. These results suggest that the half-the-sites reactivity observed in PPAT crystal structures may be pH dependent. In light of previous studies on the regulation of CoA biosynthesis, the PPAT kinetic and ligand binding data suggest that intracellular PhP concentrations modulate the distribution of PPAT monomers between high- and low-affinity CoA binding modes. This model is consistent with PPAT serving as a “backup” regulator of pathway flux relative to pantothenate kinase. 相似文献
996.
Pritchard TJ Parvatiyar M Bullard DP Lynch RM Lorenz JN Paul RJ 《American journal of physiology. Heart and circulatory physiology》2007,293(2):H1172-H1182
The Na(+)-K(+)-ATPase (NKA) is a transmembrane protein that sets and maintains the electrochemical gradient by extruding three Na(+) in exchange for two K(+). An important physiological role proposed for vascular smooth muscle NKA is the regulation of blood pressure via modulation of vascular smooth muscle contractility (5). To investigate the relations between the level of NKA in smooth muscle and blood pressure, we developed mice carrying a transgene for either the NKA alpha(1)- or alpha(2)-isoform (alpha(1 sm+) or alpha(2 sm+) mice) driven by the smooth muscle-specific alpha-actin promoter SMP8. Interestingly, both alpha-isoforms, the one contained in the transgene and the one not contained, were increased to a similar degree at both protein and mRNA levels. The total alpha-isoform protein was increased from 1.5-fold (alpha(1 sm+) mice) to 7-fold (alpha(2 sm+) mice). The increase in total NKA alpha-isoform protein was accompanied by a 2.5-fold increase in NKA activity in alpha(2 sm+) gastric antrum. Immunocytochemistry of the alpha(1)- and alpha(2)-isoforms in alpha(2 sm+) aortic smooth muscle cells indicated that alpha-isoform distributions were similar to those shown in wild-type cells. alpha(2 sm+) Mice (high expression) were hypotensive (109.9 +/- 1.6 vs. 121.3 +/- 1.4 mmHg; n = 13 and 11, respectively), whereas alpha(1 sm+) mice (low expression) were normotensive (122.7 +/- 2.5 vs. 117.4 +/- 2.3; n = 11 or 12). alpha(2 sm+) Aorta, but not alpha(1 sm+) aorta, relaxed faster from a KCl-induced contraction than wild-type aorta. Our results show that smooth muscle displays unique coordinate expression of the alpha-isoforms. Increasing smooth muscle NKA decreases blood pressure and is dependent on the degree of increased alpha-isoform expression. 相似文献
997.
Stiff CM Zhong M Sarver RW Gao H Ho AM Sweeney MT Zurenko GE Romero DL 《Bioorganic & medicinal chemistry letters》2007,17(19):5479-5482
Previously we reported the discovery and initial optimization of a novel anthranilic acid derived class of antibacterial agents which suffered from extensive protein binding. This report describes efforts directed toward understanding the relationship of the acidity of the carboxylic acid with the extent of protein binding. The pK(a) of the acid was modified via the synthesis of a number of anthranilic acid analogs which vary the aromatic ring substituent at the 4-position. The pK(a) and HSA binding constants have been determined for each of the analogs. Our results indicate a correlation between pK(a) and HSA K(d). The physical properties and antibacterial activities will be discussed as well as how these results help address the protein binding issue with this series of compounds. 相似文献
998.
Franciskovich JB Masters JJ Weber WW Klimkowski VJ Chouinard M Sipes PR Johnson LM Snyder DW Chastain MK Craft TJ Towner RD Gifford-Moore DS Froelich LL Smallwood JK Foster RS Smith GF Liebeschuetz JW Murray CW Young SC 《Bioorganic & medicinal chemistry letters》2007,17(24):6910-6913
Several P4 domain derivatives of the general d-phenylglycinamide-based scaffold (2) were synthesized and evaluated for their ability to bind to the serine protease factor Xa. Some of the more potent compounds were evaluated for their anticoagulant effects in vitro. A select subset containing various P1 indole constructs was further evaluated for their pharmacokinetic properties after oral administration to rats. 相似文献
999.
Tamagnan GD Brenner E Alagille D Staley JK Haile C Koren A Early M Baldwin RM Tarazi FI Baldessarini RJ Jarkas N Goodman MM Seibyl JP 《Bioorganic & medicinal chemistry letters》2007,17(2):533-537
A series of reboxetine analogs was synthesized and evaluated for in vitro binding as racemic mixtures. The best candidate (INER) was synthesized as the optically pure (S,S) enantiomer, labeled with iodine-123 and its in vivo binding determined by SPECT imaging in baboons. The in vivo specificity, selectivity, and kinetics of [123I]INER make it a promising agent for imaging NET in vivo by noninvasive SPECT imaging. 相似文献
1000.
Calabrese RL 《Current biology : CB》2007,17(4):R139-R141
Are central motor networks composed of task-specific dedicated neurons or are the neurons multifunctional, entering shifting coalitions for particular tasks to form different functional networks? Recent experiments elegantly indicate the latter. 相似文献