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101.
Mimicry of human IgE epitopes by anti-idiotypic antibodies 总被引:4,自引:0,他引:4
Vogel M Miescher S Kuhn S Zürcher AW Stadler MB Ruf C Effenberger F Kricek F Stadler BM 《Journal of molecular biology》2000,298(5):729-735
According to Jerne's network hypothesis, the binding site of an anti-idiotypic antibody also represents the internal image of an epitope present on a foreign, or even a self antigen. In recent years, antigen mimicry has been defined at the molecular level for some xeno-antigens. However, until now there has been no demonstration of structural mimicry between a human anti-idiotypic antibody and a self structure. To address this question, we used human IgE as the self structure and a well-defined anti-human IgE mAb (BSW17). We describe the isolation of two anti- idiotypic antibodies specific for the anti-IgE antibody BSW17 from a non-immune human Fab phage display library. Interestingly, these two anti-idiotypic antibodies mimic the same molecular surface region as a previously described IgE peptide mimotope isolated by panning on BSW17, but they cover a much larger epitope on the IgE molecule. Accordingly, immunisation of rabbits with the two anti-idiotypic antibodies induced high-affinity antibodies with the same characteristics as BSW17. Thus, our data demonstrate that it is possible to isolate anti-idiotypic antibodies derived from the human genome without the need for hyperimmunization, and confirm Jerne's hypothesis that both foreign antigens and self structures can be mimicked by our own immunoglobulins. 相似文献
102.
103.
Elsässer A Decker E Kostin S Hein S Skwara W Müller KD Greiber S Schaper W Klövekorn WP Schaper J 《Molecular and cellular biochemistry》2000,213(1-2):17-28
Recently, we proposed the hypothesis that a vicious cycle exists in human hibernating myocardium (HM) between the progression of myocyte degeneration and the development of fibrosis [1]. We now investigated the pathomechanism of this cycle in more detail and established a correlation between the severity of the morphological changes and the degree of postoperative functional recovery of HM.HM was diagnosed by dobutamine echocardiography, thallium-201 scintigraphy and radionuclide ventriculography. Functional recovery was present at 3 months after coronary bypass surgery but remained unchanged at 15 months. Forty patients were subdivided into 2 groups: A with complete and B with incomplete recovery. Biopsies taken during surgery and studied by electron microscopy, immunocytochemistry, rt-PCR, and morphometry revealed myocyte degeneration and inflammatory and fibrinogenic changes in a widened interstitial space. We report here for the first time an upregulation of TGF-1 evident by a 5-fold increase of fibroblasts and macrophages exhibiting a TGF-1 content 3-fold larger than in control, and a > 3-fold increase in TGF-1 mRNA by rt-PCR. The number of angiotensin converting enzyme (ACE) containing structures was increased (n/mm2: control - 11.4, A - 17.6, B - 19.2, control vs. A and B, p < 0.05). Fibrosis was more severe in group B than A or control (%: C - 10.1; A - 21.2; B - 40.6; p < 0.05). Capillary density was significantly reduced (n/mm2: C - 1152; A - 782; B - 579, p < 0.05) and intercapillary distance was widened (m: C - 29.5, A - 36.1, B - 43.3, p < 0.05). The number of CD 3 (n/mm2: C - 5.0; A - 9.6; B - 9.4, ns) and CD 68 positive cells (n/mm2: C - 37.2; A - 80.7; B - 55.0, C vs. A p < 0.05) was elevated in HM as compared to control indicating an inflammatory reaction. Cut-off points for functional recovery are fibrosis > 32%, capillary density < 660/mm2 and intercapillary distance > 39.0 m.In HM a self-perpetuating vicious cycle of tissue alterations leads to progressive replacement fibrosis and continuous intracellular degeneration which should be interrupted by early revascularization. 相似文献
104.
Sherson SM Hemmann G Wallace G Forbes S Germain V Stadler R Bechtold N Sauer N Smith SM 《The Plant journal : for cell and molecular biology》2000,24(6):849-857
The aim of this study was to investigate the in vivo properties and function of the high-affinity monosaccharide/proton symporter AtSTP1 of Arabidopsis. We isolated an Atstp1 knock-out mutant and found that this plant grows and develops normally. The AtSTP1 gene is expressed in germinating seeds and seedlings, with AtSTP1 activity found mainly in the seedling root. The rate of uptake of [(14)C]-3-O-methylglucose and [(14)C]-D-glucose is 60% less in Atstp1 seedlings than in the wild type, showing that AtSTP1 is the major monosaccharide transporter in Arabidopsis seedlings. Transport of D-galactose and D-mannose is also up to 60% less in Atstp1 seedlings compared to wild type, but transport of D-fructose, L-arabinose and sucrose is not reduced. Germination of Atstp1 seed shows reduced sensitivity to D-mannose, demonstrating that AtSTP1 is active before germination. Atstp1 seedlings grow effectively on concentrations of D-galactose that inhibit wild-type growth, even at up to 100 mM D-galactose, indicating that active transport by AtSTP1 plays a major role at very high concentrations of exogenous sugar. These findings provide insight into the physiological function of AtSTP1 and clearly establish its importance in the uptake of extracellular sugars by the embryo and in seedlings. 相似文献
105.
In the absence of added Fe2+, the ATPase activity of isolatedSchizosaccharomyces pombe plasma membranes (5–7 μmolP
i per mg protein per min) is moderately inhibited by H2O2 in a concentration-dependent manner. Sizable inactivation occurs only at 50–80 mmol/L H2O2. The process, probably a direct oxidative action of H2O2 on the enzyme, is not induced by the indigenous membrane-bound iron (19.3 nmol/mg membrane protein), is not affected by the
radical scavengers mannitol and Tris, and involves a decrease of both theK
m of the enzyme for ATP and theV of ATP splitting. On exposing the membranes to the Fenton reagent (50 μmol/L Fe2+ +20 mmol/L H2O2), which causes a fast production of HO− radicals, the ATPase is 50–60% inactivated and 90% of added Fe2+ is oxidized to Fe3+ within 1 min. The inactivation occurs only when Fe2+ is added before H2O2 and can thus bind to the membranes. The lack of effect of radical scavengers (mannitol, Tris) indicates that HO− radicals produced in the bulk phase play no role in inactivation. Blockage of the inactivation by the iron chelator deferrioxamine
implies that the process requires the presence of Fe2+ ions bound to binding sites on the enzyme molecules. Added catalase, which competes with Fe2+ for H2O2, slows down the inactivation but in some cases increases its total extent, probably due to the formation of the superoxide
radical that gives rise to delayed HO− production. 相似文献
106.
Peter R. Wills Stuart A. Kauffman Barbel M. R. Stadler Peter F. Stadler 《Bulletin of mathematical biology》1998,60(6):1073-1098
The theory of autocatalytic binary ligation is reviewed within the context of a consistently applied Michaelis-Menten quasi-steady-state
approximation to obtain explicit analytical results describing time-course data from experiments. A detailed protocol for
the step-wise elucidation of a minimal set of experimental parameters is outlined. The kinetic equations are then generalized
to cases of self-and cross-catalysis among an arbitrary number of different templates and applied to experiments involving
just two templates. Depending on the values of various kinetic parameters such systems can display exclusionary Darwinian
selection corresponding to an exponential growth law, selective coexistence or coexistence of all species characteristic of
a parabolic growth law; the intermediate behaviour arises as a property of the full mechanism analysed here. Our results are
applicable to the classical case of self-replicating nucleic acids and their analogues as well as to newly discovered self-replicating
peptides. 相似文献
107.
Nicolas Favre Claudia Daubenberger Jutta Marfurt Alberto Moreno Manuel Patarroyo G. Pluschke 《Immunogenetics》1998,48(4):253-259
We cloned and sequenced TcR alpha chain cDNA of three healthy Aotus nancymaae monkeys. Fifteen different TRAJ segments and 9 different TRAV genes were identified in the 29 rearrangements analyzed. As expected from the greater phylogenetic distance, A. nancymaae TRA gene sequences diverged more from the human sequences than those of the chimpanzee or the rhesus macaque. However, no Aotus TRAJ segment or TRAV gene was found which lacked a human counterpart. These counterparts were AJ02, AJ05, AJ09, AJ15, AJ22, AJ23, AJ28, AJ30, AJ32, AJ34, AJ37, AJ40, AJ42, AJ45, AJ52 and AV2S1, AV2S3, AV3S1, AV8S1, AV12S1, AV15S1, ADV21S1/DV5, AV22S1S and AV23S1, respectively. In most cases the identity of amino acid sequences between corresponding Aotus and human genes was greater than 80%. This marked conservation of TRA gene sequences indicates a close structural relationship of Aotus and human TcR and demonstrates that the TcR repertoire in primates is remarkably stable. The results support the concept
of using Aotus monkeys, which are susceptible to infection with the human malaria parasite Plasmodium falciparum, as an animal model for the evaluation of molecularly defined malaria vaccine candidates.
Received: 15 January 1998 / Revised: 23 March 1998 相似文献
108.
In a seminatural manipulation experiment with artificial irrigation we followed throughfall and forest floor solution chemistry collected underneath aphid infested and uninfested Norway spruce. Solutions underneath infested trees showed significantly higher concentrations of dissolved organic carbon (DOC) but lower concentrations of dissolved organic nitrogen (DON), NO3 -N, and NH4 -N in throughfall solutions and of NH4 -N in forest floor solutions. Average concentrations were 40.5% (DON), 27.5% (NO3 -N), and 46.2% lower (NH4 -N) underneath infested trees in throughfall solutions, and 19.5% (DON), 9.4% (NO3 -N), and 42.0% (NH4 -N) lower in forest floor solutions. Differences in throughfall were more pronounced than in forest floor leachates. It is likely that honeydew is fuelling the metabolism of micro-organisms and thus critically affects above and below ground nutrient cycles. We emphasize the importance of linking the biology of herbivores and micro-organisms with geochemical processes. 相似文献
109.
Many properties of organisms show great robustness against mutations. Whether this robustness is an evolved property or intrinsic to genetic systems is by and large unknown. An evolutionary origin of robustness would require a rethinking of key concepts in the field of molecular evolution, such as gene-specific neutral mutation rates, or the context-independence of deleterious mutations. We provide evidence that mutational robustness of the genome of RNA viruses to mutational changes in secondary structure has evolved. J. Exp. Zool. ( Mol. Dev. Evol.) 285:119-127, 1999. 相似文献
110.