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91.
92.
93.
Constantin Rüder Tobias Haase Annalena Krost Nicole Langwieser Jan Peter Stefanie Kamann Dietlind Zohlnh?fer 《PloS one》2014,9(8)
Aims
Several studies suggest that circulating bone marrow derived stem cells promote the regeneration of ischemic tissues. For hematopoietic stem cell transplantation combinatorial granulocyte-colony stimulating factor (G-CSF)/Plerixafor (AMD3100) administration was shown to enhance mobilization of bone marrow derived stem cells compared to G-CSF monotherapy. Here we tested the hypothesis whether combinatorial G-CSF/AMD3100 therapy has beneficial effects in cardiac recovery in a mouse model of myocardial infarction.Methods
We analyzed the effect of single G-CSF (250 µg/kg/day) and combinatorial G-CSF/AMD3100 (100 µg/kg/day) treatment on cardiac morphology, vascularization, and hemodynamics 28 days after permanent ligation of the left anterior descending artery (LAD). G-CSF treatment started directly after induction of myocardial infarction (MI) for 3 consecutive days followed by a single AMD3100 application on day three after MI in the G-CSF/AMD3100 group. Cell mobilization was assessed by flow cytometry of blood samples drawn from tail vein on day 0, 7, and 14.Results
Peripheral blood analysis 7 days after MI showed enhanced mobilization of white blood cells (WBC) and endothelial progenitor cells (EPC) upon G-CSF and combinatorial G-CSF/AMD3100 treatment. However, single or combinatorial treatment showed no improvement in survival, left ventricular function, and infarction size compared to the saline treated control group 28 days after MI. Furthermore, no differences in histology and vascularization of infarcted hearts could be observed.Conclusion
Although the implemented treatment regimen caused no adverse effects, our data show that combinatorial G-CSF/AMD therapy does not promote myocardial regeneration after permanent LAD occlusion. 相似文献94.
C Ramos I Sch?dtler-Siwon L Ortiz-Ortiz 《Journal of immunology (Baltimore, Md. : 1950)》1979,122(4):1243-1247
Infection with Trypanosoma cruzi decreases the ability of spleen cells from mice to respond to either T cell, concanavalin A (Con A), or B cell, lipopolysaccharide (LPS), mitogens. The effect of infection on the mitogenic response depends on the elapsed time between the day of infection and the time of mitogen presentation. Responses early in infection are normal, whereas later responses to either mitogen are depressed. Spleen cells from late trypanosome-infected mice inhibit the ability of normal spleen cells to respond to Con A or LPS. The cell in the T. cruzi-infected spleen cells responsible for this effect is nonadherent, sensitive to treatment with anti-mouse thymus serum plus complement, but insensitive to treatment with anti-immunoglobulin plus complement. These data indicate that infection with T. cruzi elicits over time the generation of T cells suppressive to T and B cell mitogenic responses. 相似文献
95.
96.
Mukhran Khundadze Katrin Kollmann Nicole Koch Christoph Biskup Sandor Nietzsche Geraldine Zimmer J. Christopher Hennings Antje K. Huebner Judit Symmank Amir Jahic Elena I. Ilina Kathrin Karle Ludger Sch?ls Michael Kessels Thomas Braulke Britta Qualmann Ingo Kurth Christian Beetz Christian A. Hübner 《PLoS genetics》2013,9(12)
Hereditary spastic paraplegias (HSPs) are characterized by progressive weakness and spasticity of the legs because of the degeneration of cortical motoneuron axons. SPG15 is a recessively inherited HSP variant caused by mutations in the ZFYVE26 gene and is additionally characterized by cerebellar ataxia, mental decline, and progressive thinning of the corpus callosum. ZFYVE26 encodes the FYVE domain-containing protein ZFYVE26/SPASTIZIN, which has been suggested to be associated with the newly discovered adaptor protein 5 (AP5) complex. We show that Zfyve26 is broadly expressed in neurons, associates with intracellular vesicles immunopositive for the early endosomal marker EEA1, and co-fractionates with a component of the AP5 complex. As the function of ZFYVE26 in neurons was largely unknown, we disrupted Zfyve26 in mice. Zfyve26 knockout mice do not show developmental defects but develop late-onset spastic paraplegia with cerebellar ataxia confirming that SPG15 is caused by ZFYVE26 deficiency. The morphological analysis reveals axon degeneration and progressive loss of both cortical motoneurons and Purkinje cells in the cerebellum. Importantly, neuron loss is preceded by accumulation of large intraneuronal deposits of membrane-surrounded material, which co-stains with the lysosomal marker Lamp1. A density gradient analysis of brain lysates shows an increase of Lamp1-positive membrane compartments with higher densities in Zfyve26 knockout mice. Increased levels of lysosomal enzymes in brains of aged knockout mice further support an alteration of the lysosomal compartment upon disruption of Zfyve26. We propose that SPG15 is caused by an endolysosomal membrane trafficking defect, which results in endolysosomal dysfunction. This appears to be particularly relevant in neurons with highly specialized neurites such as cortical motoneurons and Purkinje cells. 相似文献
97.
Many mountain ranges have been strongly glaciated during the Quaternary ice ages, and the locations of glacial refugia of mountain plants have been debated for a long time. A series of detailed molecular studies, investigating intraspecific genetic variation of mountain plants in the European Alps, now allows for a first synopsis. A comparison of the phylogeographic patterns with geological and palaeoenvironmental data demonstrates that glacial refugia were located along the southwestern, southern, eastern and northern border of the Alps. Additional glacial refugia were present in central Alpine areas, where high-elevation plants survived the last glaciation on ice-free mountain tops. The observed intraspecific phylogeographies suggest general patterns of glacial survival, which conform to well-known centres of Alpine species diversity and endemism. This implies that evolutionary or biogeographic processes induced by climatic fluctuations act on gene and species diversity in a similar way. 相似文献
98.
99.
Longin CF Utz HF Reif JC Schipprack W Melchinger AE 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2006,112(5):903-912
Optimum allocation of resources is of fundamental importance for the efficiency of breeding programs. The objectives of our
study were to (1) determine the optimum allocation for the number of lines and test locations in hybrid maize breeding with
doubled haploids (DHs) regarding two optimization criteria, the selection gain ΔG
k
and the probability P
k
of identifying superior genotypes, (2) compare both optimization criteria including their standard deviations (SDs), and
(3) investigate the influence of production costs of DHs on the optimum allocation. For different budgets, number of finally
selected lines, ratios of variance components, and production costs of DHs, the optimum allocation of test resources under
one- and two-stage selection for testcross performance with a given tester was determined by using Monte Carlo simulations.
In one-stage selection, lines are tested in field trials in a single year. In two-stage selection, optimum allocation of resources
involves evaluation of (1) a large number of lines in a small number of test locations in the first year and (2) a small number
of the selected superior lines in a large number of test locations in the second year, thereby maximizing both optimization
criteria. Furthermore, to have a realistic chance of identifying a superior genotype, the probability P
k
of identifying superior genotypes should be greater than 75%. For budgets between 200 and 5,000 field plot equivalents, P
k
> 75% was reached only for genotypes belonging to the best 5% of the population. As the optimum allocation for P
k
(5%) was similar to that for ΔG
k
, the choice of the optimization criterion was not crucial. The production costs of DHs had only a minor effect on the optimum
number of locations and on values of the optimization criteria.
C. Friedrich H. Longin and H. Friedrich Utz contributed equally to this work. 相似文献
100.
Pragl B Koschak A Trieb M Obermair G Kaufmann WA Gerster U Blanc E Hahn C Prinz H Schütz G Darbon H Gruber HJ Knaus HG 《Bioconjugate chemistry》2002,13(3):416-425
Hongotoxin(1) (HgTX(1)), a 39-residue peptide recently isolated from the venom of Centruroides limbatus, blocks the voltage-gated K+ channels K(v)1.1, K(v)1.2, and K(v)1.3 at picomolar toxin concentrations (Koschak, A., Bugianesi, R. M., Mitterdorfer, J., Kaczorowski, G. J., Garcia, M. L., and Knaus, H. G. (1998) J. Biol. Chem. 273, 2639-2644). In this report, we determine the three-dimensional structure of HgTX(1) using NMR spectroscopy (PDB-code: 1HLY). HgTX(1) was found to possess a structure similar to previously characterized K+ channel toxins (e.g. margatoxin) consisting of a three-stranded antiparallel beta-sheet (residues 2-4, 26-30, and 33-37) and a helical conformation (part 3(10) helix and part alpha helix; residues 10-20). Due to the importance of residue Lys-28 for high-affinity interaction with the respective channels, lysine-reactive fluorescence dyes cannot be used to label wild-type HgTX(1). On the basis of previous studies (see above) and our NMR data, a HgTX(1) mutant (HgTX(1)-A19C) was engineered, expressed, and purified. HgTX(1)-A19C-SH was labeled using sulfhydryl-reactive Cy3-, Cy5-, and Alexa-dyes. Pharmacological characterization of fluorescently labeled HgTX(1)-A19C in radioligand binding studies indicated that these hongotoxin(1) analogues retain high-affinity for voltage-gated K+ channels and a respective pharmacological profile. Cy3- and Alexa-dye-labeled hongotoxin(1) analogues were used to investigate the localization of K+ channels in brain sections. The distribution of toxin binding closely follows the distribution of K(v)1.2 immunoreactivity with the highest expression levels in the cerebellar Purkinje cell layer. Taken together, these results demonstrate that fluorescently labeled HgTX(1) analogues comprise novel probes to characterize a subset of voltage-gated K+ channels. 相似文献