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971.
Nafe R Glienke W Burgemeister R Gangnus R Haar B Pries A Schlote W 《Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology》2004,26(2):65-76
OBJECTIVE: To study the regional heterogeneity of epidermal growth factor receptor (EGFR) gene amplification (EGFR-GA) in glioblastomas, considering the relationship between this mutation and morphology of tumor cell nuclei. STUDY DESIGN: Tissue samples gained by laser microdissection and pressure catapulting were used for the performance of differential polymerase chain reaction in 32 morphologically different regions from 7 glioblastomas. Semiquantitative determination of EGFR expression and image analysis of tumor cell nuclei were performed in the same regions. RESULTS: Distinct regional differences concerning the degree of EGFR-GA were found in 2 tumor cases. When comparing regions with different degrees of gene amplification within these cases, morphologic differences in tumor cell nuclei were observed. The other tumor cases also showed distinct intratumoral heterogeneity concerning histomorphology but no regional heterogeneity in the degree of EGFR-GA. When comparing regions with a low densitometric EGFR/interferon (INF) band ratio (< 2.19, n = 18) and a high EGFR/IFN band ratio (> 4.39, n = 14), the latter type of region showed a significantly higher percentage of Ki-67--positive tumor cell nuclei and lower values for several shape variables (Fourier amplitudes), indicating a tendency toward a more regular nuclear shape in regions with distinct EGFR-GA. For the EGFR/IFN band ratio, a significant correlation was found with several morphometric variables, especially those of nuclear shape and distances between nuclei. CONCLUSION: In glioblastomas showing regional heterogeneity in the degree of EGFR-GA, morphology of tumor cell nuclei has been shown to be different when comparing regions with different degrees of EGFR-GA. Glioblastomas may also show distinct regional heterogeneity of histomorphology without evidence of regional heterogeneity of EGFR-GA. A significant statistical association has been confirmed between the degree of EGFR-GA and quantitative morphology of tumor cell nuclei. 相似文献
972.
Xu YL Reinscheid RK Huitron-Resendiz S Clark SD Wang Z Lin SH Brucher FA Zeng J Ly NK Henriksen SJ de Lecea L Civelli O 《Neuron》2004,43(4):487-497
Arousal and anxiety are behavioral responses that involve complex neurocircuitries and multiple neurochemical components. Here, we report that a neuropeptide, neuropeptide S (NPS), potently modulates wakefulness and could also regulate anxiety. NPS acts by activating its cognate receptor (NPSR) and inducing mobilization of intracellular Ca2+. The NPSR mRNA is widely distributed in the brain, including the amygdala and the midline thalamic nuclei. Central administration of NPS increases locomotor activity in mice and decreases paradoxical (REM) sleep and slow wave sleep in rats. NPS was further shown to produce anxiolytic-like effects in mice exposed to four different stressful paradigms. Interestingly, NPS is expressed in a previously undefined cluster of cells located between the locus coeruleus (LC) and Barrington's nucleus. These results indicate that NPS could be a new modulator of arousal and anxiety. They also show that the LC region encompasses distinct nuclei expressing different arousal-promoting neurotransmitters. 相似文献
973.
Bertini I Felli IC Kümmerle R Luchinat C Pierattelli R 《Journal of biomolecular NMR》2004,30(3):245-251
13C-13C NOESY experiments were performed under long mixing time conditions on reduced human superoxide dismutase (32 kDa, 15N, 13C and 70% 2H labeled). 13C-13C couplings were successfully eliminated through post-processing of in-phase-anti-phase (IPAP) data. It appears that at mixing time m of 3.0 s the spin diffusion mechanism allows the detection of 96% of the two-bond correlations involving C and C. The interpretation was confirmed by simulations. This approach broadens the range of applicability of 13C-13C NOESY spectroscopy. 相似文献
974.
Wessely R Paschalidis M Wagenpfeil S Wegener F Neumann FJ Theiss W 《American journal of physiology. Heart and circulatory physiology》2004,287(6):H2461-H2467
The role of metabolic factors derived from cardiac muscle in the development of reactive hyperemia after brief occlusions of the coronary circulation seems to be well established. However, the contribution of occlusion-induced changes in hemodynamic forces to eliciting reactive hyperemia is less known. We hypothesized that in isolated coronary arterioles changes in intraluminal pressure and flow, during and after release of occlusion (O/R), themselves via activating intrinsic mechanosensitive mechanisms, elicit release of vasoactive factors resulting in reactive dilations. Thus in isolated coronary arterioles (diameter: 88 +/- 8 microm) changes in diameter to changes in pressure or pressure plus flow (P+F) during and after a brief period (30, 60, and 120 s) of O/R of cannulating tube were measured by videomicroscopy. In response to both types of O/R, diameter first decreased, then, subsequently increased during occlusions. When only pressure was changed (from 80-10-80 mmHg), after release of occlusion, peak dilations increased as a function of the duration of occlusions. After flow was established (30 microl/min), O/R elicited changes in both pressure and flow (from 80-10-80 mmHg and from 0 to 30 microl/min). In these conditions, after the release of occlusions, not only the peak but also the duration of reactive dilation increased significantly as a function of the length of occlusions. The dilations during, and peak dilations after occlusions both in pressure and P+F protocols were significantly reduced by the inhibition of NO synthase with Nomega-nitro-L-arginine-methyl-ester (L-NAME) or by endothelium removal, whereas duration of postocclusion dilations were reduced by L-NAME or by endothelium removal only in P+F protocols. Furthermore, in both protocols, catalase significantly reduced the peak but not the duration of reactive dilations. Thus, mechanosensitive mechanisms that are sensitive to deformation, pressure, stretch, and wall shear stress elicit release of NO and H2O2, resulting in reactive dilation of isolated coronary arterioles. 相似文献
975.
Bade-Doeding C Elsner HA Eiz-Vesper B Seltsam A Holtkamp U Blasczyk R 《Immunogenetics》2004,56(2):83-88
In this study we have sequenced peptides eluted from a truncated recombinant HLA-A*6602 molecule, and compared their features with data reported for peptides presented in the A*6601 molecule. A striking change in the amino-acid binding preferences was observed at peptide position P1, which interacts with pocket A of the HLA peptide-binding region. For A*6601, aspartic acid and glutamic acid, both of which possess polar acidic side-chains, have been described as auxiliary anchors. This is in marked contrast to A*6602, where we observed serine, which has a neutral polar side-chain, as auxiliary anchor at P1. Accordingly, this shift in the physico-chemical properties of the auxiliary anchor may be best explained by the HLA amino-acid polymorphism at position 163, where arginine (hydrophilic, alkaline) in A*6601 has been replaced by glutamic acid in A*6602. This amino-acid exchange results in a shift towards higher acidity in pocket A, apparently resulting in the loss of preference for acidic auxiliary anchors, and leading to the preference for the neutral amino acid serine. The change of the auxiliary anchor residue at P1 is likely to alter the spectrum of peptides presented by A*6602 compared with A*6601, which may result in allogenicity in the case of a mismatch in allogeneic stem cell transplantation. 相似文献
976.
Differential antiviral response of endothelial cells after infection with pathogenic and nonpathogenic hantaviruses 总被引:9,自引:0,他引:9
Kraus AA Raftery MJ Giese T Ulrich R Zawatzky R Hippenstiel S Suttorp N Krüger DH Schönrich G 《Journal of virology》2004,78(12):6143-6150
Hantaviruses represent important human pathogens and can induce hemorrhagic fever with renal syndrome (HFRS), which is characterized by endothelial dysfunction. Both pathogenic and nonpathogenic hantaviruses replicate without causing any apparent cytopathic effect, suggesting that immunopathological mechanisms play an important role in pathogenesis. We compared the antiviral responses triggered by Hantaan virus (HTNV), a pathogenic hantavirus associated with HFRS, and Tula virus (TULV), a rather nonpathogenic hantavirus, in human umbilical vein endothelial cells (HUVECs). Both HTNV- and TULV-infected cells showed increased levels of molecules involved in antigen presentation. However, TULV-infected HUVECs upregulated HLA class I molecules more rapidly. Interestingly, HTNV clearly induced the production of beta interferon (IFN-beta), whereas expression of this cytokine was barely detectable in the supernatant or in extracts from TULV-infected HUVECs. Nevertheless, the upregulation of HLA class I on both TULV- and HTNV-infected cells could be blocked by neutralizing anti-IFN-beta antibodies. Most strikingly, the antiviral MxA protein, which interferes with hantavirus replication, was already induced 16 h after infection with TULV. In contrast, HTNV-infected HUVECs showed no expression of MxA until 48 h postinfection. In accordance with the kinetics of MxA expression, TULV replicated only inefficiently in HUVECs, whereas HTNV-infected cells produced high titers of virus particles that decreased after 48 h postinfection. Both hantavirus species, however, could replicate equally well in Vero E6 cells, which lack an IFN-induced MxA response. Thus, delayed induction of antiviral MxA in endothelial cells after infection with HTNV could allow viral dissemination and contribute to the pathogenesis leading to HFRS. 相似文献
977.
Saedler R Mathur N Srinivas BP Kernebeck B Hülskamp M Mathur J 《Plant & cell physiology》2004,45(7):813-822
In Arabidopsis, based on the randomly misshapen phenotype of leaf epidermal trichomes, eight genes have been grouped into a 'DISTORTED' class. Three of the DIS genes, WURM, DISTORTED1 and CROOKED have been cloned recently and encode the ARP2, ARP3 and ARPC5 subunits respectively, of a conserved actin modulating ARP2/3 complex. Here we identify a fourth gene, DISTORTED2 as the Arabidopsis homolog of the ARPC2 subunit of the ARP2/3 complex. Like other mutants in the complex dis2 trichomes also display supernumerary, randomly localized cortical actin patches. In addition dis2 trichomes possess abnormally clustered endoplasmic microtubules near sites of actin aggregation. Since microtubules are strongly implicated in the establishment and maintenance of growth directionality in higher plants our observations of aberrant microtubule clustering in dis2 trichomes suggests a convincing explanation for the randomly distorted trichome phenotype in dis mutants. In addition, the close proximity of microtubule clusters to the arbitrarily dispersed cortical actin patches in the dis mutants provides fresh insights into cytoskeletal interactions leading us to suggest that in higher plants microtubule arrangements directed towards the establishment and maintenance of polar growth-directionality are guided by cortical actin behavior and organization. 相似文献
978.
979.
Long-term inhibition by auxin of leaf blade expansion in bean and Arabidopsis 总被引:1,自引:0,他引:1
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The role of auxin in controlling leaf expansion remains unclear. Experimental increases to normal auxin levels in expanding leaves have shown conflicting results, with both increases and decreases in leaf growth having been measured. Therefore, the effects of both auxin application and adjustment of endogenous leaf auxin levels on midrib elongation and final leaf size (fresh weight and area) were examined in attached primary monofoliate leaves of the common bean (Phaseolus vulgaris) and in early Arabidopsis rosette leaves. Aqueous auxin application inhibited long-term leaf blade elongation. Bean leaves, initially 40 to 50 mm in length, treated once with alpha-naphthalene acetic acid (1.0 mm), were, after 6 d, approximately 80% the length and weight of controls. When applied at 1.0 and 0.1 mm, alpha-naphthalene acetic acid significantly inhibited long-term leaf growth. The weak auxin, beta-naphthalene acetic acid, was effective at 1.0 mm; and a weak acid control, benzoic acid, was ineffective. Indole-3-acetic acid (1 microm, 10 microm, 0.1 mm, and 1 mm) required daily application to be effective at any concentration. Application of the auxin transport inhibitor, 1-N-naphthylphthalamic acid (1% [w/w] in lanolin), to petioles also inhibited long-term leaf growth. This treatment also was found to lead to a sustained elevation of leaf free indole-3-acetic acid content relative to untreated control leaves. Auxin-induced inhibition of leaf growth appeared not to be mediated by auxin-induced ethylene synthesis because growth inhibition was not rescued by inhibition of ethylene synthesis. Also, petiole treatment of Arabidopsis with 1-N-naphthylphthalamic acid similarly inhibited leaf growth of both wild-type plants and ethylene-insensitive ein4 mutants. 相似文献
980.
Neugebauer R Betz H Kuhse J 《Biochemical and biophysical research communications》2003,305(3):476-483
Glycine is an essential co-agonist of the excitatory N-methyl-D-aspartate (NMDA) receptor. The glycine binding site of this subtype of ionotropic glutamate receptors is formed by the S1 and S2 regions of the NR1 subunit. Here, different S1S2 fusion proteins were expressed and purified from Escherichia coli cultures, and refolding protocols were established allowing the production of 30 mg of soluble S1S2 fusion protein from 1 liter bacterial culture. After affinity purification and renaturation, two of the fusion proteins (S1S2 and S1S2-V1) bound the competitive glycine site antagonist [3H]MDL105,519 with K(d) values of 9.35 and 3.9 nM, respectively. In contrast, with three other constructs (S1S2M, S1S2-V2, and -V3) saturable ligand binding could not be obtained. These results redefine the S1S2 domains required for high-affinity glycine binding. Furthermore, our high-affinity binding proteins may be used for the large-scale production of the glycine binding core region for future structural studies. 相似文献