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991.
992.
Òscar Palacios Ayelen Pagani Sílvia Pérez-Rafael Margit Egg Martina Höckner Anita Brandstätter Mercè Capdevila Sílvia Atrian Reinhard Dallinger 《BMC biology》2011,9(1):4
Background
The degree of metal binding specificity in metalloproteins such as metallothioneins (MTs) can be crucial for their functional accuracy. Unlike most other animal species, pulmonate molluscs possess homometallic MT isoforms loaded with Cu+ or Cd2+. They have, so far, been obtained as native metal-MT complexes from snail tissues, where they are involved in the metabolism of the metal ion species bound to the respective isoform. However, it has not as yet been discerned if their specific metal occupation is the result of a rigid control of metal availability, or isoform expression programming in the hosting tissues or of structural differences of the respective peptides determining the coordinative options for the different metal ions. In this study, the Roman snail (Helix pomatia) Cu-loaded and Cd-loaded isoforms (HpCuMT and HpCdMT) were used as model molecules in order to elucidate the biochemical and evolutionary mechanisms permitting pulmonate MTs to achieve specificity for their cognate metal ion. 相似文献993.
994.
Schneider EM Flacke S Liu F Lorenz MR Schilling P Nass ME Foehr KJ Huber-Lang M Weiss ME 《Journal of cell communication and signaling》2011,5(2):145-156
Severe trauma and the systemic inflammatory response syndrome (SIRS) occur as a result of a cytokine storm which is in part
due to ATP released from damaged tissue. This pathology also leads to increased numbers of immature antigen presenting cells
(APC) sharing properties of dendritic cells (DC) or macrophages (MΦ). The occurrence of immature APC appears to coincide with
the reactivation of herpes virus infections such as Epstein Barr virus (EBV). The aim of this study was the comparative analysis
of the ultrastructural and functional characteristics of such immature APC. In addition, we investigated EBV infection/ reactivation
and whether immature APC might be targets for natural killers (NK). Significant macroautophagy, mitochondrial degradation
and multivesicular body formation together with the identification of herpes virus particles were morphological findings associated
with immature APC. Exogenous stressors such as ATP further increased morphological signs of autophagy, including LC3 expression.
Functional tests using fluorescent bacteria proved impaired phagolysosome fusion. However, immature APC were susceptible to
NK-92-mediated cytolysis. We found evidence for EBV latency state II infection by detecting EBV-specific LMP1 and EBNA2 in
immature APC and in whole blood of these patients. In summary, trauma-induced cytokine storms may induce maturation arrest
of APC, promote ATP-induced autophagy, support EBV persistence and impair the degradation of phagocytozed bacteria through
inefficient phagolysosome fusion. The susceptibility to NK-mediated cytolysis supports the hypothesis that NK function is
likely to contribute to immune reconstitution after major trauma by regulating immature APC, and ATP-induced autophagy and
survival. 相似文献
995.
Quantification of optic disc edema during exposure to high altitude shows no correlation to acute mountain sickness 总被引:1,自引:0,他引:1
Willmann G Fischer MD Schatz A Schommer K Messias A Zrenner E Bartz-Schmidt KU Gekeler F 《PloS one》2011,6(11):e27022
Background
The study aimed to quantify changes of the optic nerve head (ONH) during exposure to high altitude and to assess a correlation with acute mountain sickness (AMS). This work is related to the Tuebingen High Altitude Ophthalmology (THAO) study.Methodology/Principal Findings
A confocal scanning laser ophthalmoscope (cSLO, Heidelberg Retina Tomograph, HRT3®) was used to quantify changes at the ONH in 18 healthy participants before, during and after rapid ascent to high altitude (4559 m). Slitlamp biomicroscopy was used for clinical optic disc evaluation; AMS was assessed with Lake Louise (LL) and AMS-cerebral (AMS-c) scores; oxygen saturation (SpO2) and heart rate (HR) were monitored. These parameters were used to correlate with changes at the ONH. After the first night spent at high altitude, incidence of AMS was 55% and presence of clinical optic disc edema (ODE) 79%. Key stereometric parameters of the HRT3® used to describe ODE (mean retinal nerve fiber layer [RNFL] thickness, RNFL cross sectional area, optic disc rim volume and maximum contour elevation) changed significantly at high altitude compared to baseline (p<0.05) and were consistent with clinically described ODE. All changes were reversible in all participants after descent. There was no significant correlation between parameters of ODE and AMS, SpO2 or HR.Conclusions/Significance
Exposure to high altitude leads to reversible ODE in the majority of healthy subjects. However, these changes did not correlate with AMS or basic physiologic parameters such as SpO2 and HR. For the first time, a quantitative approach has been used to assess these changes during acute, non-acclimatized high altitude exposure. In conclusion, ODE presents a reaction of the body to high altitude exposure unrelated to AMS. 相似文献996.
Background
ETV6/RUNX1 (E/R) (also known as TEL/AML1) is the most frequent gene fusion in childhood acute lymphoblastic leukemia (ALL) and also most likely the crucial factor for disease initiation; its role in leukemia propagation and maintenance, however, remains largely elusive. To address this issue we performed a shRNA-mediated knock-down (KD) of the E/R fusion gene and investigated the ensuing consequences on genome-wide gene expression patterns and deducible regulatory functions in two E/R-positive leukemic cell lines.Findings
Microarray analyses identified 777 genes whose expression was substantially altered. Although approximately equal proportions were either up- (KD-UP) or down-regulated (KD-DOWN), the effects on biological processes and pathways differed considerably. The E/R KD-UP set was significantly enriched for genes included in the “cell activation”, “immune response”, “apoptosis”, “signal transduction” and “development and differentiation” categories, whereas in the E/R KD-DOWN set only the “PI3K/AKT/mTOR signaling” and “hematopoietic stem cells” categories became evident. Comparable expression signatures obtained from primary E/R-positive ALL samples underline the relevance of these pathways and molecular functions. We also validated six differentially expressed genes representing the categories “stem cell properties”, “B-cell differentiation”, “immune response”, “cell adhesion” and “DNA damage” with RT-qPCR.Conclusion
Our analyses provide the first preliminary evidence that the continuous expression of the E/R fusion gene interferes with key regulatory functions that shape the biology of this leukemia subtype. E/R may thus indeed constitute the essential driving force for the propagation and maintenance of the leukemic process irrespective of potential consequences of associated secondary changes. Finally, these findings may also provide a valuable source of potentially attractive therapeutic targets. 相似文献997.
998.
999.
The alpha-helical coiled coil can adopt a variety of topologies, among the most common of which are parallel and antiparallel dimers and trimers. We present Multicoil2, an algorithm that predicts both the location and oligomerization state (two versus three helices) of coiled coils in protein sequences. Multicoil2 combines the pairwise correlations of the previous Multicoil method with the flexibility of Hidden Markov Models (HMMs) in a Markov Random Field (MRF). The resulting algorithm integrates sequence features, including pairwise interactions, through multinomial logistic regression to devise an optimized scoring function for distinguishing dimer, trimer and non-coiled-coil oligomerization states; this scoring function is used to produce Markov Random Field potentials that incorporate pairwise correlations localized in sequence. Multicoil2 significantly improves both coiled-coil detection and dimer versus trimer state prediction over the original Multicoil algorithm retrained on a newly-constructed database of coiled-coil sequences. The new database, comprised of 2,105 sequences containing 124,088 residues, includes reliable structural annotations based on experimental data in the literature. Notably, the enhanced performance of Multicoil2 is evident when tested in stringent leave-family-out cross-validation on the new database, reflecting expected performance on challenging new prediction targets that have minimal sequence similarity to known coiled-coil families. The Multicoil2 program and training database are available for download from http://multicoil2.csail.mit.edu. 相似文献
1000.
Balabanova Y Gilsdorf A Buda S Burger R Eckmanns T Gärtner B Gross U Haas W Hamouda O Hübner J Jänisch T Kist M Kramer MH Ledig T Mielke M Pulz M Stark K Suttorp N Ulbrich U Wichmann O Krause G 《PloS one》2011,6(10):e25691