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61.
Chemokines presented on specialized endothelial surfaces rapidly up-regulate leukocyte integrin avidity and firm arrest through G(i)-protein signaling. Here we describe a novel, G-protein-independent, down-regulatory activity of apical endothelial chemokines in destabilizing L-selectin-mediated leukocyte rolling. Unexpectedly, this anti-adhesive chemokine suppression of rolling does not involve L-selectin shedding. Destabilization of rolling is induced only by immobilized chemokines juxtaposed to L-selectin ligands and is an energy-dependent process. Chemokines are found to interfere with a subsecond stabilization of selectin tethers necessary for persistent rolling. This is a first indication that endothelial chemokines can attenuate in situ L-selectin adhesion to endothelial ligands at subsecond contacts. This negative feedback mechanism may underlie the jerky nature of rolling mediated by L-selectin in vivo. 相似文献
62.
To gain insight into the mechanism by which the alpha(M)I-domain of integrin alpha(M)beta(2) interacts with multiple and unrelated ligands, the identity of the neutrophil inhibitory factor (NIF) recognition site was sought. A systematic strategy in which individual amino acid residues within three previously implicated segments were changed to those in the alpha(L)I-domain, which is structurally very similar but does not bind NIF, was implemented. The capacity of the resulting mutants, expressed as glutathione S-transferase fusion proteins, to recognize NIF was assessed. These analyses ultimately identified Asp(149), Arg(151), Gly(207), Tyr(252), and Glu(258) as critical for NIF binding. Cation binding, a function of the metal ion-dependent adhesion site (MIDAS) motif, was assessed by terbium luminescence to evaluate conformational perturbations induced by the mutations. All five mutants bound terbium with unaltered affinities. When the five residues were inserted into the alpha(L)I-domain, the chimera bound NIF with high affinity. Another ligand of alpha(M)beta(2), C3bi, which is known to use the same segments of the alpha(M)I-domain in engaging the receptor, failed to bind to the chimeric alpha(L)I-domain. Thus, the alpha(M)I-domain appears to present a mosaic of exposed amino acids within surface loops on its MIDAS face, and different ligands interact with different residues to attain high affinity binding. 相似文献
63.
Vidalain PO Laine D Zaffran Y Azocar O Servet-Delprat C Wild TF Rabourdin-Combe C Valentin H 《Journal of virology》2002,76(13):6415-6424
In the thymus, epithelial cells comprise a heterogeneous population required for the generation of functional T lymphocytes, suggesting that thymic epithelium disruption by viruses may compromise T-cell lymphopoiesis in this organ. In a previous report, we demonstrated that in vitro, measles virus induced differentiation of cortical thymic epithelial cells as characterized by (i) cell growth arrest, (ii) morphological and phenotypic changes, and (iii) apoptotis as a final step of this process. In the present report, we have analyzed the mechanisms involved. First, measles virus-induced differentiation of thymic epithelial cells is shown to be strictly dependent on beta interferon (IFN-beta) secretion. In addition, transfection with double-stranded RNA, a common intermediate of replication for a broad spectrum of viruses, is reported to similarly mediate thymic epithelial cell differentiation through IFN-beta induction. Finally, we demonstrated that recombinant IFN-alpha, IFN-beta, or IFN-gamma was sufficient to induce differentiation and apoptosis of uninfected thymic epithelial cells. These observations suggested that interferon secretion by either infected cells or activated leukocytes, such as plasmacytoid dendritic cells or lymphocytes, may induce thymic epithelium disruption in a pathological context. Thus, we have identified a new mechanism that may contribute to thymic atrophy and altered T-cell lymphopoiesis associated with many infections. 相似文献
64.
Stefanov K Nechev J Lavchieva-Nacheva G Nikolova N Seizova K Kwartirnikov M Lavchiev V Popov S 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2002,131(3):543-550
Total lipid, fatty acid and sterol composition of larvae and adults of Musca domestica was investigated before and after feeding on sucrose syrup or on the same syrup containing 1% lead nitrate. The effects of sucrose and of lead ions were found to be different. In larvae sucrose diet inhibited the fatty acid elongation and stimulated the first stages of their unsaturation. A significant increase of phytosterol concentrations was obtained. These changes increased the cell membrane permeability. The addition of lead caused a decrease of the fatty acid unsaturation, which decreased the cell membrane permeability. In adults the sucrose diet had no effect on the lipid and sterol composition, while the addition of lead decreased the cholesterol concentration. The composition of lipids and sterols also depends on the diet of larvae before pupation. The data obtained suggested that changes in lipid and sterol composition, which control the permeability of the cell membrane, might be an adaptive response of the organism to the changes of the environment. 相似文献
65.
A database comprising all ligand-binding sites of known structure aligned with all related protein sequences and structures is described. Currently, the database contains approximately 50000 ligand-binding sites for small molecules found in the Protein Data Bank (PDB). The structure-structure alignments are obtained by the Combinatorial Extension (CE) program (Shindyalov and Bourne, Protein Eng., 11, 739-747, 1998) and sequence-structure alignments are extracted from the ModBase database of comparative protein structure models for all known protein sequences (Sanchez et al., Nucleic Acids Res., 28, 250-253, 2000). It is possible to search for binding sites in LigBase by a variety of criteria. LigBase reports summarize ligand data including relevant structural information from the PDB file, such as ligand type and size, and contain links to all related protein sequences in the TrEMBL database. Residues in the binding sites are graphically depicted for comparison with other structurally defined family members. LigBase provides a resource for the analysis of families of related binding sites. 相似文献
66.
Extrinsic control of developmental diapause in nymphs of prostriate ticks of the subgenus Ixodes sensu stricto (Ixodes ricinus and Ixodes persulcatus from Eurasia and Ixodes scapularis from North America) appears to be based on a complex two-step photoperiodic reaction of a short-day/long-day type. Diapause
control in the subgenus Afrixodes (the South African tick Ixodes rubicundus) appears to be based on a simple long-day reaction. The option between non-diapause development and diapausing arrest in
engorged nymphs is determined by both pre- and post-feeding photoperiodic regimes. Consequently diapausing arrest in engorged
nymphs of Ixodes sensu stricto can be induced either by a short-day (after their engorgement) or by a long-day regime (in unfed nymphs), while active, non-diapause
development is possible only when the short-day pre-feeding regime is followed by a long-day post-feeding regime. The photoperiodic
response in I. (Afrixodes) rubicundus nymphs seems to be of the long-day type both before and after feeding. Consequently this non-diapause development is enabled
by a long-day regime, while diapause is induced by a short-day regime of exposure. Nevertheless, there are some indications
that the control of nymphal diapause in the latter species is also of a complex nature.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
67.
Dragoi V 《Biological cybernetics》2002,86(6):419-426
Simple exposure to repeatitive stimulation is known to induce short-term learning effects across a wide range of species.
These effects can be both suppressive and facilitatory depending on stimulus conditions: repeatitive presentation of a weak
stimulus decreases the strength of the response (habituation), whereas presentation of a tonic stimulus following a series
of weak stimuli transiently increases the response strength (dishabituation). Although these phenomena have been comprehensively
characterized at both behavioral and cellular levels, most existing models of nonassociative learning focus exclusively on
the suppressive or facilitatory changes in response, and do not attempt to relate cellular events to behavior. I propose here
a feedforward model of habituation effects that explains both suppressive and facilitatory changes in response relying on
the interaction between excitatory and inhibitory processes that develop in parallel on two different timescales. The model's
properties are used to explain the rate sensitivity property of habituation and recovery and stimulus dishabituation.
Received: 1 June 2001 / Accepted in revised form: 4 December 2001 相似文献
68.
The cholinergic anti-inflammatory pathway: a missing link in neuroimmunomodulation 总被引:18,自引:0,他引:18
Pavlov VA Wang H Czura CJ Friedman SG Tracey KJ 《Molecular medicine (Cambridge, Mass.)》2003,9(5-8):125-134
This review outlines the mechanisms underlying the interaction between the nervous and immune systems of the host in response to an immune challenge. The main focus is the cholinergic anti-inflammatory pathway, which we recently described as a novel function of the efferent vagus nerve. This pathway plays a critical role in controlling the inflammatory response through interaction with peripheral a7 subunit-containing nicotinic acetylcholine receptors expressed on macrophages. We describe the modulation of systemic and local inflammation by the cholinergic anti-inflammatory pathway and its function as an interface between the brain and the immune system. The clinical implications of this novel mechanism also are discussed. 相似文献
69.
Li Y Johnson G Romine JL Meanwell NA Martin SW Dworetzky SI Boissard CG Gribkoff VK Starrett JE 《Bioorganic & medicinal chemistry letters》2003,13(8):1437-1439
Electrophysiological evaluation of symmetrical analogues of the known maxi-K opener NS-004 (1) led to the discovery of bisphenols 2a, 3a and 4a as openers of cloned maxi-K channels expressed in oocytes. 相似文献
70.
Rodrigues MF Valentin HE Berger PA Tran M Asrar J Gruys KJ Steinbüchel A 《Applied microbiology and biotechnology》2000,53(4):453-460
Burkholderia sp. accumulates polyhydroxyalkanoates (PHAs) containing 3-hydroxybutyrate and 3-hydroxy-4-pentenoic acid when grown on mineral
media under limited phosphate or nitrogen, and using sucrose or gluconate as a carbon and energy source. Solvent fractionation
and NMR spectroscopic characterization of these polyesters revealed the simultaneous accumulation of two homopolyesters rather
than a co-polyester with random sequence distribution of the monomers [Valentin HE, Berger PA, Gruys KJ, Rodrigues MFA, Steinbüchel
A, Tran M, Asrar J (1999) Macromolecules 32: 7389–7395]. To understand the genetic requirements for such unusual polyester
accumulation, we probed total genomic DNA from Burkholderia sp. by Southern hybridization experiments using phaC-specific probes. These experiments indicated the presence of more than one PHA synthase gene within the genome of Burkholderia sp. However, when total genomic DNA from Burkholderia sp. was used to complement a PHA-negative mutant of Ralstonia eutropha for PHA accumulation, only one PHA synthase gene was obtained resembling the R. eutropha type of PHA synthases, based on amino acid sequence similarity. In addition to the PHA synthase gene, based on high sequence
homology, genes encoding a β-ketothiolase and acetoacetyl-CoA reductase were identified in a gene cluster with the PHA synthase
gene. The arrangement of the three genes is quite similar to the R. eutropha poly-β-hydroxybutyrate biosynthesis operon.
Received: 3 September 1999 / Received revision: 29 October 1999 / Accepted: 5 November 1999 相似文献