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121.
Flagella and cilia are two very similar organelles that "beat" to move cells and to propel fluid over tissues. They are highly conserved, being found in organisms ranging from prokaryotes to plant and animal eukaryotes. In humans, cilia are present in almost every organ, and several human conditions involve dysfunctional cilia; for example, lateralization defects, where the positions of organs are reversed, and primary ciliary dyskinesia, a rare condition where patients suffer from recurrent respiratory infections. In this article, we will discuss how information gained from studies on algae has aided research into these human diseases. These studies found a variety of functions that was previously unsuspected, renewing interest in cilia. 相似文献
122.
123.
Bélanger LF Roy S Tremblay M Brott B Steff AM Mourad W Hugo P Erikson R Charron J 《Molecular and cellular biology》2003,23(14):4778-4787
MEK is a dual-specificity kinase that activates the extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase upon agonist binding to receptors. The ERK/MAP kinase cascade is involved in cell fate determination in many organisms. In mammals, this pathway is proposed to regulate cell growth and differentiation. Genetic studies have shown that although a single Mek gene is present in Caenorhabditis elegans, Drosophila melanogaster, and Xenopus laevis, two Mek homologs, Mek1 and Mek2, are present in the mammalian cascade. The inactivation of the Mek1 gene leads to embryonic lethality and has revealed the unique role played by Mek1 during embryogenesis. To investigate the biological function of the second homolog, we have generated mice deficient in Mek2 function. Mek2 mutant mice are viable and fertile, and they do not present flagrant morphological alteration. Although several components of the ERK/MAP kinase cascade have been implicated in thymocyte development, no such involvement was observed for MEK2, which appears to be nonessential for thymocyte differentiation and T-cell-receptor-induced proliferation and apoptosis. Altogether, our findings demonstrate that MEK2 is not necessary for the normal development of the embryo and T-cell lineages, suggesting that the loss of MEK2 can be compensated for by MEK1. 相似文献
124.
Potential differences were assessed between the dominant (D) and non-dominant (ND) forearms of sedentary subjects during anaerobic exercise. Subjects performed voluntary concentric contractions of D and ND forearm muscle during a series of three high-intensity (60% of the maximal voluntary contraction force (MVC)) exercise bouts. The time-dependent changes in intracellular pH (pH(i)), Pi, and PCr concentrations, and their relation to muscular work were examined using 31P magnetic resonance spectroscopy (MRS) techniques, and revealed that D forearm metabolic kinetics in sedentary individuals are improved during repetitive high-intensity exercise compared to their respective ND forearm muscle. We postulate that the more regular and preferential utilization of the D limb leads to a "trained-like" condition. 相似文献
125.
Enterococcus faecium clinical isolate BM4524, resistant to vancomycin and susceptible to teicoplanin, harboured a chromosomal vanB cluster, including the vanSB/vanRB two-component system regulatory genes. Enterococcus faecium strain BM4525, isolated two weeks later from the same patient, was resistant to high levels of both glycopeptides. The ddl gene of BM4525 had a 2 bp insertion leading to an impaired d-alanine:d-alanine ligase. Sequencing of the vanB operon in BM4525 also revealed an 18 bp deletion in the vanSB gene designated vanSBDelta. The resulting six amino acid deletion partially overlapped the G2 ATP-binding domain of the VanSBDelta histidine kinase leading to constitutive expression of the resistance genes. Sequence analysis indicated that the deletion occurred between two tandemly arranged heptanucleotide direct repeats, separated by 11 base-pairs. The VanSB, VanSBDelta and VanRB proteins were overproduced in Escherichia coli and purified. In vitro autophosphorylation of the VanSB and VanSBDelta histidine kinases and phosphotransfer to the VanRB response regulator did not differ significantly. However, VanSBDelta was deficient in VanRB phosphatase activity leading to accumulation of phosphorylated VanRB. Increased glycopeptide resistance in E. faecium BM4525 was therefore a result of the lack of production of d-alanyl-d-alanine ending pentapeptide and to constitutive synthesis of d-alanyl-d-lactate terminating peptidoglycan precursors, following loss of d-alanine:d-alanine ligase and of VanSB phosphatase activity respectively. We suggest that the heptanucleotide direct repeat in vanSB may favour the appearance of high level constitutively expressed vancomycin resistance through a 'slippage' type of genetic rearrangement in VanB-type strains. 相似文献
126.
Floch V Delépine P Guillaume C Loisel S Chassé S Le Bolc'h G Gobin E Leroy JP Férec C 《Biochimica et biophysica acta》2000,1464(1):95-103
Performances of cationic lipid formulations for intravenous gene delivery to mouse lungs have been previously reported. We report in this study that cationic phosphonolipids, when appropriately formulated, can be good synthetic vectors for gene delivery to lung after intravenous administration. One of our reagents, GLB43, was capable of mediating a 500-fold higher expression in the lungs of mice than could be obtained with free pDNA alone (P=0.018). We demonstrate that the most important parameters for cationic phosphonolipid transfection activity after systemic administration are the chemical structure of the cationic phosphonolipid, the lipid to DNA charge ratio and the inclusion of co-lipid in the formulation. We report using a luciferase reporter gene that transfection activity in vivo 24 h after cationic phosphonolipid systemic administration could not be predicted from in vitro analysis. In contrast to in vitro studies, cationic phosphonolipids including the oleyl acyl chains (GLB43) were more effective than its analogue with the myristyl acyl chains (GLB73). Using pathological analysis of animal livers, we demonstrate that the toxicity level was correlated with the lipoplex formulation and the lipid to DNA ratio. 相似文献
127.
Clumping factor B (ClfB), a new surface-located fibrinogen-binding adhesin of Staphylococcus aureus 总被引:6,自引:3,他引:3
Déirdre Ní Eidhin Samuel Perkins Patrice Francois Pierre Vaudaux Magnus Höök & Timothy J. Foster 《Molecular microbiology》1998,30(2):245-257
The surface-located fibrinogen-binding protein (clumping factor; ClfA) of Staphylococcus aureus has an unusual dipeptide repeat linking the ligand binding domain to the wall-anchored region. Southern blotting experiments revealed several other loci in the S. aureus Newman genome that hybridized to a probe comprising DNA encoding the dipeptide repeat. One of these loci is analysed here. It also encodes a fibrinogen-binding protein, which we have called ClfB. The overall organization of ClfB is very similar to that of ClfA, and the proteins have considerable sequence identity in the signal sequence and wall attachment domains. However, the A regions are only 26% identical. Recombinant biotinylated ClfB protein bound to fibrinogen in Western ligand blots. ClfB reacted with the α- and β-chains of fibrinogen in the ligand blots in contrast to ClfA, which binds exclusively to the γ-chain. Analysis of proteins released from the cell wall of S. aureus Newman by Western immunoblotting using antibody raised against the recombinant A region of ClfB identified a 124 kDa protein as the clfB gene product. This protein was detectable only on cells that were grown to the early exponential phase. It was absent from cells from late exponential phase or stationary phase cultures. Using a clfB mutant isolated by allelic replacement alone and in combination with a clfA mutation, the ClfB protein was shown to promote (i) clumping of exponential-phase cells in a solution of fibrinogen, (ii) adherence of exponential-phase bacteria to immobilized fibrinogen in vitro, and (iii) bacterial adherence to ex vivo human haemodialysis tubing, suggesting that it could contribute to the pathogenicity of biomaterial-related infections. However, in wild-type exponential-phase S. aureus Newman cultures, ClfB activity was masked by the ClfA protein, and it did not contribute at all to interactions of cells from stationary-phase cultures with fibrinogen. ClfB-dependent bacterial adherence to immobilized fibrinogen was inhibited by millimolar concentrations of Ca2+ and Mn2+, which indicates that, like ClfA, ligand binding by ClfB is regulated by a low-affinity inhibitory cation binding site. 相似文献
128.
The medial-Golgi Ion Pump Pmr1 Supplies the Yeast Secretory Pathway with Ca2+ and Mn2+ Required for Glycosylation, Sorting, and Endoplasmic Reticulum-Associated Protein Degradation 下载免费PDF全文
Gabriele Dürr Jochen Strayle Richard Plemper Saskia Elbs Saskia K. Klee Patrice Catty Dieter H. Wolf Hans K. Rudolph 《Molecular biology of the cell》1998,9(5):1149-1162
The yeast Ca2+ adenosine triphosphatase Pmr1, located in medial-Golgi, has been implicated in intracellular transport of Ca2+ and Mn2+ ions. We show here that addition of Mn2+ greatly alleviates defects of pmr1 mutants in N-linked and O-linked protein glycosylation. In contrast, accurate sorting of carboxypeptidase Y (CpY) to the vacuole requires a sufficient supply of intralumenal Ca2+. Most remarkably, pmr1 mutants are also unable to degrade CpY*, a misfolded soluble endoplasmic reticulum protein, and display phenotypes similar to mutants defective in the stress response to malfolded endoplasmic reticulum proteins. Growth inhibition of pmr1 mutants on Ca2+-deficient media is overcome by expression of other Ca2+ pumps, including a SERCA-type Ca2+ adenosine triphosphatase from rabbit, or by Vps10, a sorting receptor guiding non-native luminal proteins to the vacuole. Our analysis corroborates the dual function of Pmr1 in Ca2+ and Mn2+ transport and establishes a novel role of this secretory pathway pump in endoplasmic reticulum-associated processes. 相似文献
129.
Pierre Verhaeghe Nadine Azas Sébastien Hutter Caroline Castera-Ducros Michèle Laget Aurélien Dumètre Monique Gasquet Jean-Pierre Reboul Sylvain Rault Pascal Rathelot Patrice Vanelle 《Bioorganic & medicinal chemistry》2009,17(13):4313-4322
To identify a new safe antiplasmodial molecular scaffold, an original series of 2-trichloromethylquinazolines, functionalized in position 4 by an alkyl- or arylamino substituent, was synthesized from 4-chloro-2-trichloromethylquinazoline 1, via a cheap, fast and efficient solvent-free operating procedure. Among the 40 molecules prepared, several exhibit a good profile with both a significant antiplasmodial activity on the W2 Plasmodium falciparum strain (IC50 values: 0.4–2.2 μM) and a promising toxicological behavior regarding human cells (HepG2/W2 selectivity indexes: 40–83), compared to the antimalarial drug compounds chloroquine and doxycycline. The in vitro antitoxoplasmic and antileishmanial evaluations were conducted in parallel on the most active molecules, showing that these ones specifically display antiplasmodial properties. 相似文献
130.
Joy Perrier Patrice Clochon Fran?oise Bertran Colette Couque Jan Bulla Pierre Denise Marie-Laure Bocca 《PloS one》2015,10(1)