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961.
962.
Chemical engineering of the peptidyl transferase center reveals an important role of the 2'-hydroxyl group of A2451
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Erlacher MD Lang K Shankaran N Wotzel B Hüttenhofer A Micura R Mankin AS Polacek N 《Nucleic acids research》2005,33(5):1618-1627
The main enzymatic reaction of the large ribosomal subunit is peptide bond formation. Ribosome crystallography showed that A2451 of 23S rRNA makes the closest approach to the attacking amino group of aminoacyl-tRNA. Mutations of A2451 had relatively small effects on transpeptidation and failed to unequivocally identify the crucial functional group(s). Here, we employed an in vitro reconstitution system for chemical engineering the peptidyl transferase center by introducing non-natural nucleosides at position A2451. This allowed us to investigate the peptidyl transfer reaction performed by a ribosome that contained a modified nucleoside at the active site. The main finding is that ribosomes carrying a 2′-deoxyribose at A2451 showed a compromised peptidyl transferase activity. In variance, adenine base modifications and even the removal of the entire nucleobase at A2451 had only little impact on peptide bond formation, as long as the 2′-hydroxyl was present. This implicates a functional or structural role of the 2′-hydroxyl group at A2451 for transpeptidation. 相似文献
963.
Falet H Chang G Brohard-Bohn B Rendu F Hartwig JH 《American journal of physiology. Cell physiology》2005,289(4):C819-C825
Cofilin, in its Ser3 dephosphorylated form, accelerates actin filament turnover in cells. We report here the role of cofilin in platelet actin assembly. Cofilin is primarily phosphorylated in the resting platelet as evidenced by a specific antibody directed against its Ser3 phosphorylated form. After stimulation with thrombin under nonstirring conditions, cofilin is reversibly dephosphorylated and transiently incorporates into the actin cytoskeleton. Its dephosphorylation is maximal 12 min after platelet stimulation, shortly after the peak of actin assembly occurs. Cofilin rephosphorylation begins 2 min after activation and exceeds resting levels by 510 min. Cofilin is dephosphorylated with identical kinetics but fails to become rephosphorylated when platelets are stimulated under stirring conditions. Cofilin is normally rephosphorylated when platelets are stimulated in the presence of Arg-Gly-Asp-Ser (RGDS) peptide or wortmannin to block IIb3 cross-linking and signaling or in platelets isolated from a patient with Glanzmann thrombasthenia, which express only 23% of normal IIb3 levels. Furthermore, actin assembly and Arp2/3 complex incorporation in the platelet actin cytoskeleton are decreased when IIb3 is engaged. Our results suggest that cofilin is essential for actin dynamics mediated by outside-in signals in activated platelets. 相似文献
964.
Lawson SR Gabra BH Guérin B Neugebauer W Nantel F Battistini B Sirois P 《Regulatory peptides》2005,124(1-3):221-224
The vascular complications associated with type 1 diabetes are to some extent related to the dysfunction of the endothelium leading to an increased vascular permeability and plasma extravasation in the surrounding tissues. The various micro- and macro-vascular complications of diabetes develop over time, leading to nephropathy, retinopathy and neuropathy and cardiomyopathy. In the present study, the effect of a novel selective bradykinin B1 receptor (BKB1-R) antagonist, R-954, was investigated on the changes of vascular permeability in the skin and retina of streptozotocin (STZ)-induced type 1 diabetic rats. Plasma extravasation increased in the skin and retina of STZ-diabetic rats after 1 week and persisted over 4 weeks following STZ injection. Acute treatment with R-954 (2 mg/kg, bolus s.c.) highly reduced the elevated vascular permeability in both 1- and 4-week STZ-diabetic rats. These results showed that the inducible BKB1-R subtype modulates the vascular permeability of the skin and retina of type 1 diabetic rats and suggests that BKB1-R antagonists could have a beneficial role in diabetic neuropathy and retinopathy. 相似文献
965.
Quantitative analyses of animal motion are increasingly easy to conduct using simple video equipment and relatively inexpensive software packages. With careful use, such analytical tools have the potential to quantify differences in movement between individuals or species and to allow insights into the behavioral consequences of morphological differences between taxa. However, as with any other type of measurement, there are errors associated with kinematic measurements. Because normative kinematic data on human and nonhuman primate locomotion are used to model aspects of gait of fossil hominins, errors in the extant data influence the accuracy of fossil gait reconstructions. The principal goal of this paper is to illustrate the effect of camera speeds (frame rates) on kinematic measurement errors, and to demonstrate how these errors vary with subject size, movement velocity, and sample size. Kinematic data for human walking and running (240 Hz), as well as data for primate quadrupedal walking and running (180 Hz) were used as inputs for a simulation of the measurement errors associated with various linear and temporal kinematic variables. Measurement errors were shown to increase as camera speed, subject body size, and interval duration all decrease, and as movement velocity increases. These results have implications for the methods used to calculate subject velocity and suggest that using a moving marker to measure the linear displacements of the body is preferable to the use of a stationary marker. Finally, while slower camera speeds will always result in higher measurement errors than do faster camera speeds, this effect can be moderated to some extent by collecting sufficiently large samples of data. 相似文献
966.
967.
Fardeau M Braun S Romero NB Hogrel JY Rouche A Ortega V Mourot B Squiban P Benveniste O Herson S 《Journal de la Société de Biologie》2005,199(1):29-32
This is the first gene transfer trial in Duchenne/Becker patients. The aim of the study was to provide evidence on transgene expression and safety of the intramuscular administration of a plasmid containing a full-length dystrophin CDNA. Nine Duchenne/Becker patients, distributed in three cohorts of three patients, were injected into their radialis muscles either once with 200 microg (first cohort) or 600 microg (second cohort) or twice, two weeks apart, with 600 microg plasmidic DNA (third cohort). The patients were enrolled sequentially upon evaluation of the data by an independant pilot committee. In the biopsies taken three weeks after the initial injection from the injected site, the plasmid was detected in all patients. An exogenous dystrophin expression was found in 6/9 patients. The level of expression was low, up to 6 % of weak complete sarcolemmal labelling, and up to 26% of partial sarcolemmal staining. Dystrophin in RNAs were detected by nested RT-PCR in five out of the six biopsies with exogenous dystrophin-positive fibers. Interestingly, neither humoral or cellular antidystrophin responses were observed. No local or general adverse effects were seen. This paves the way for future developments in gene therapy in hereditary muscle diseases, and specifically in Duchenne/Becker myopathies. 相似文献
968.
Leptodora kindtii, a pelagic predatory cladoceran, suffers high mortality on transfer to laboratory, which makes the experimental work difficult. We investigated the causes of high mortality, using four variables: water volume, animal density, light intensity, and origin of water for culturing, i.e., water from native or a non-native lake. For the experiments we used Leptodora and water from Lake Loosdrecht and Lake Maarsseveen (The Netherlands). Water was found to be the most important factor; the animals did not necessarily do better in lake water from which they were collected. Water volume and animal density were of limited importance, and light intensity did not affect survival. 相似文献
969.
970.
SOX9 is a sex-determining factor which induces Sertoli cell differentiation and subsequent testis cord formation. It is expressed both in male and female undifferentiated gonads in the cytoplasmic compartment of pre-Sertoli cells. At the time of sexual differentiation, SOX9 moves into the nucleus of male pre-Sertoli cells whereas in female, it remains in the cytoplasm and then its expression decreases. To study the cytoplasmic localization of SOX9, we have analyzed its interaction with the cytoskeleton components. By treatment of NT2/D1 and transfected NIH3T3 cell lines and embryonic gonads with nocodazole, a drug depolymerizing the microtubules, we show that cytoplasmic retention of SOX9 requires the integrity of the microtubule network. Using biochemical experiments, we demonstrated that SOX9 is able to interact with microtubules in vitro and in vivo. On the other hand, we observed a complete male-specific reorganization of the microtubule network in epithelial Sertoli cells of the male embryonic gonad at the time of sexual differentiation and testis cord formation. 相似文献