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91.
Breck Byers 《The Journal of cell biology》1966,30(3):C1-C6
92.
Andrew S. Felts Alice L. Rodriguez Ryan D. Morrison Anna L. Blobaum Frank W. Byers J. Scott Daniels Colleen M. Niswender P. Jeffrey Conn Craig W. Lindsley Kyle A. Emmitte 《Bioorganic & medicinal chemistry letters》2018,28(10):1679-1685
Based on previous work that established fused heterocycles as viable alternatives for the picolinamide core of our lead series of mGlu5 negative allosteric modulators (NAMs), we designed a novel series of 6-(pyrimidin-5-ylmethyl)quinoline-8-carboxamide mGlu5 NAMs. These new quinoline derivatives also contained carbon linkers as replacements for the diaryl ether oxygen atom common to our previously published chemotypes. Compounds were evaluated in a cell-based functional mGlu5 assay, and an exemplar analog 27 was >60-fold selective versus the other seven mGlu receptors. Selected compounds were also studied in metabolic stability assays in rat and human S9 hepatic fractions and exhibited a mixture of P450- and non-P450-mediated metabolism. 相似文献
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94.
Effects of lidocaine on axonal morphology,microtubules, and rapid transport in rabbit vagus In vitro
Margaret R. Byers B. Raymond Fink Ross D. Kennedy Mical E. Middaugh Anita E. Hendrickson 《Developmental neurobiology》1973,4(2):125-143
Treatment with lidocaine, at exposures which completely block impulse conduction and rapid axonal transport, resulted in a sequence of morphological effects on rabbit vagus never in vitro. Low exposures (0.3% for 90 min, 0.4% for 45 min, 0.6% for 25 min) caused a reorientation and proliferation of smooth endoplasmic reticulum (SER); the number of axonal microtubules either remained normal or was increased. Intermediate exposures (0.4% for 90 min, 0.6% for 45 min) Produced a similar effect on the SER, as well as causing a 50% reduction in microtubule number and some swelling of axons and Schwann cells. The highest exposure (0.6% for 75 min) caused over 90% reduction in microtubule number, a partial loss of neurofilaments, and severe swelling of axons, Schwann call, and mitochondria. Reversibility of these effects was tested in lidocaine-treated nerves that had been washed with fresh culture medium. There was good recovery of nerve exposures. After intermediate exposures, there was only partial return of rapid transport, even though imposures, there was morphological, and no recovery occured throughout the excised vagus nerve in efferent and afferent axons as well as Schwann cells, and these events did not coincide with changes in the functional state of rapid axonal transport. 相似文献
95.
96.
97.
Exon-intron organization, expression, and chromosomal localization of the human motilin gene 总被引:1,自引:0,他引:1
H Yano Y Seino J Fujita Y Yamada N Inagaki J Takeda G I Bell R L Eddy Y S Fan M G Byers 《FEBS letters》1989,249(2):248-252
The human motilin gene has been isolated and characterized. The gene spans about 9 kilobase pairs (kb) and the 0.7 kb motilin mRNA is encoded by five exons. The 22-amino-acid motilin sequence is encoded by exons 2 and 3. The human motilin gene was mapped to the p21.2----p21.3 region of chromosome 6 by hybridization of the cloned cDNA to DNAs from a panel of reduced human-mouse somatic cell hybrids and by in situ hybridization to human prometaphase chromosomes. RNA blotting using RNA prepared from various regions of the human gastrointestinal tract revealed high levels of motilin mRNA in duodenum and lower levels in the antrum of the stomach; motilin mRNA could not be detected by this procedure in the esophagus, cardia of the stomach, descending colon or gallbladder. 相似文献
98.
Externalization of phosphatidylserine (PtdSer) is a common feature of programmed cell death and plays an important role in the recognition and removal of apoptotic cells. In this study with U937 cells, PtdSer synthesis from [(3)H]serine was stimulated and newly synthesized PtdSer was transferred preferentially to cell-free medium vesicles (CFMV) from cells when apoptosis was induced with a topoisomerase I inhibitor, camptothecin (CAM). When CAM-induced apoptosis was blocked by a caspase inhibitor, z-VAD-fmk, stimulation of PtdSer synthesis and movement to CFMV were abolished. In contrast, changes in synthesis and transport of sphingomyelin (SM) or phosphatidylethanolamine (PtdEtn) were minor; total phosphatidylcholine (PtdCho) synthesis was below control levels. All phospholipids appeared in CFMV but PtdSer displayed a 6-fold increase relative to controls compared to 3-fold for SM, 2-fold for PtdCho and 1.8-fold for PtdEtn. Even greater effects on specificity of PtdSer synthesis, movement to CFMV and inhibition by z-VAD-fmk were observed in apoptotic cells induced by UV irradiation or tumor necrosis factor-alpha/cycloheximide treatment. Thus, PtdSer biosynthesis stimulated during apoptosis in U937 cells was specific for this phospholipid and was correlated with caspase-mediated exposure of PtdSer at the cell surface and preferential movement to vesicles during apoptosis. 相似文献
99.
100.
S E Thomas S J Morris Z Xu D M Byers F B Palmer M W Spence H W Cook 《Biochimica et biophysica acta》1992,1126(2):125-134
Plasmalogens (1-O-alk-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamine) are major phospholipids in many tissues and cells, particularly of neural origin. Using cultured C6 glioma cells and subcellular fractions isolated on Percoll gradients we investigated selectivity for esterification of several polyunsaturated fatty acids (PUFA) in the sn-2 position of plasmalogens compared to [1-14C]hexadecanol, representative of de novo synthesis of the ether-linked sn-1 position. In whole cells at a final concentration of 105 microM PUFA, 2-4 nmol plasmalogen/mg protein was labeled in 4 h and 10-14 nmol in 24 h, representing 8-15% and 35-50%, respectively, of initial plasmalogen mass. Incorporation of label from hexadecanol was lower than PUFA incorporation (20:5(n-3) greater than 20:4(n-6) greater than 18:3(n-3) much greater than 18:2(n-6)) suggesting deacylation-reacylation at the sn-2 position. Plasmalogens accounted for 50% of total cell ethanolamine phospholipids and 75% in plasma membrane. Using a novel, improved method for extraction of subcellular fractions containing Percoll, plasma membrane also was enriched in plasmalogen relative to microsomes (107.4 +/- 5.2 vs. 40.0 +/- 2.9 nmol/mg protein). Selectivity for esterification at the sn-2 position of plasmalogens with respect to chain length and unsaturation of the fatty acyl chain was similar in both subcellular fractions and reflected that of whole cells. Labeling of plasma membrane with PUFA and fatty alcohol lagged behind that of microsomes. Chase experiments in cells prelabeled with [1-14C]18:3(n-3) for 2 h showed no significant reduction of label in plasmalogen of any subcellular fraction although accumulation of label in the microsomal fraction was slowed initially. Reduction of plasmalogen label (40-50%) did occur in microsomes and plasma membrane when cells prelabeled for 24 h were switched to chase medium with or without chase fatty acid. Our data suggest that esterification of PUFA to plasmalogen may occur at the endoplasmic reticulum with subsequent translocation to plasma membrane resulting in accumulation of relatively stable pools of plasmalogen that are not readily accessible for deacylation-reacylation exchange with newly appearing PUFA. Alternatively, deacylation-reacylation may occur in a more stable phospholipid pool within the plasma membrane but would involve a slower process than at the endoplasmic reticulum. 相似文献