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71.
目的:探讨初治、年轻、中高/高危弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)的临床特征、治疗措施及预后影响因素。方法:回顾性分析2006年1月至2014年5月军事医学科学院附属医院淋巴瘤科收治的年龄≤60岁、年龄调整的国际预后指数(aa IPI)评分≥2分的初治DLBCL病例,进行疗效及预后相关因素的分析。结果:共收集到资料完整的DLBCL病例120例,中位随访28(4-106)个月,3年PFS率53.25%,OS率61.52%。单因素分析结果显示B症状、治疗方案及近期疗效、自体移植对无进展生存(PFS)及总体生存(OS)率的影响有统计学意义。多因素分析结果显示治疗方案、自体造血干细胞移植是影响PFS、OS率的独立影响因素。结论:年轻、中高/高危DLBCL具有高度异质性,病理细胞来源、Ki-67等在本组病例中未见显著预后意义,有待临床进一步探索。 相似文献
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Joan Rhl Zoe E. West Maren Rudolph Andreea Zaharia Derek Van Lonkhuyzen Danica K. Hickey Annalese B. T. Semmler Rachael Z. Murray 《Traffic (Copenhagen, Denmark)》2019,20(9):661-673
Macrophage migration into injured or infected tissue is a key aspect in the pathophysiology of many diseases where inflammation is a driving factor. Membrane‐type‐1 matrix metalloproteinase (MT1‐MMP) cleaves extracellular matrix components to facilitate invasion. Here we show that, unlike the constitutive MT1‐MMP surface recycling seen in cancer cells, unactivated macrophages express low levels of MT1‐MMP. Upon lipopolysaccharide (LPS) activation, MT1‐MMP synthesis dramatically increases 10‐fold at the surface by 15 hours. MT1‐MMP is trafficked from the Golgi complex to the surface via late endosomes/lysosomes in a pathway regulated by the late endosome/lysosome R‐SNAREs VAMP7 and VAMP8. These form two separate complexes with the surface Q‐SNARE complex Stx4/SNAP23 to regulate MT1‐MMP delivery to the plasma membrane. Loss of either one of these SNAREs leads to a reduction in surface MT1‐MMP, gelatinase activity and reduced invasion. Thus, inhibiting MT1‐MMP transport through this pathway could reduce macrophage migration and the resulting inflammation. 相似文献
75.
该实验以烟草悬浮细胞 BY 2 为材料,在烟草悬浮细胞中分别加入0.05、0.10、0.15、0.20 mmol·L-1AlCl3,以等体积去离子水处理的悬浮细胞液为对照,并依据前述实验结果选择0.15 mmol·L-1 AlCl3,分别添加5 mmol·L-1 DMTU(H2O2 抑制剂)、20 μmol·L-1CaCl2、15 μmol·L-1 LaCl3(Ca2+通道抑制剂)和50 μmol·L-1 ATP设计多项处理,分析胞外ATP(eATP)对铝离子(Al3+)胁迫引起的植物细胞死亡及其胞内H2O2、Ca2+的影响,以揭示Al3+胁迫下植物调节细胞死亡的可能机制,进一步扩展对eATP功能的认知。结果显示:(1)随着 AlCl3 胁迫浓度的提高,细胞死亡水平和胞内H2O2水平上升,而胞内Ca2+和eATP水平则逐渐降低。(2)外援施加H2O2抑制剂 DMTU(二甲基硫脲)和Ca2+能够有效缓解AlCl3诱导的细胞死亡水平的上升;而Ca2+通道抑制剂LaCl3(三氯化镧)则加剧了AlCl3胁迫下的细胞死亡。(3)在AlCl3胁迫下对细胞添加外源ATP,能够缓解AlCl3胁迫下胞内H2O2水平上升和Ca2+水平下降的同时,并显著降低AlCl3胁迫导致的细胞死亡。研究表明, Al3+以剂量依赖的模式提升细胞死亡和细胞内H2O2的水平并降低胞内Ca2+和eATP水平,AlCl3诱导的细胞死亡受到H2O2和Ca2+水平变化的调节,eATP可以通过调节H2O2与Ca2+水平缓解AlCl3诱导的细胞死亡。推测Al3+胁迫可能通过抑制钙离子通道而破坏了细胞内H2O2和Ca2+之间的协同关系,外源ATP对Al3+诱导H2O2上升的缓解作用可能是由于其提升了细胞的抗氧化能力。 相似文献
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77.
It is now well-established that compositional bias in DNA sequences can adversely affect phylogenetic analysis based on those
sequences. Phylogenetic analyses based on protein sequences are generally considered to be more reliable than those derived
from the corresponding DNA sequences because it is believed that the use of encoded protein sequences circumvents the problems
caused by nucleotide compositional biases in the DNA sequences. There exists, however, a correlation between AT/GC bias at
the nucleotide level and content of AT- and GC-rich codons and their corresponding amino acids. Consequently, protein sequences
can also be affected secondarily by nucleotide compositional bias. Here, we report that DNA bias not only may affect phylogenetic
analysis based on DNA sequences, but also drives a protein bias which may affect analyses based on protein sequences. We present
a striking example where common phylogenetic tools fail to recover the correct tree from complete animal mitochondrial protein-coding
sequences. The data set is very extensive, containing several thousand sites per sequence, and the incorrect phylogenetic
trees are statistically very well supported. Additionally, neither the use of the LogDet/paralinear transform nor removal
of positions in the protein alignment with AT- or GC-rich codons allowed recovery of the correct tree. Two taxa with a large
compositional bias continually group together in these analyses, despite a lack of close biological relatedness. We conclude
that even protein-based phylogenetic trees may be misleading, and we advise caution in phylogenetic reconstruction using protein
sequences, especially those that are compositionally biased.
Received: 19 February 1998 / Accepted: 28 August 1998 相似文献
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79.
Aerosol delivery to the airways of the human respiratory tract, followed by absorption, constitutes an alternative route of administration for compounds unsuitable for delivery by conventional oral and parenteral routes. The target for aerosol drug delivery is the airways epithelium, i.e. tracheal, bronchial, bronchiolar and alveolar cells, which become the site of drug deposition. These epithelial layers also serve as a barrier to the penetration of inhaled material. An in vitro model for aerosol deposition and transport across epithelia in the human airways may be a good predictor of in vivo disposition. The present preliminary studies begin an investigation that blends the dynamics of aerosol delivery and the basis of an in vitro simulated lung model to evaluate the transport properties of a series of molecular weight marker compounds across human-derived bronchiolar epithelial cell monolayers. An Andersen viable cascade impactor was used as a delivery apparatus for the deposition of size-segregated particles onto monolayers of small airway epithelial cells and Calu-3 cells. It was shown that these cell layers can withstand placement in the impactor, and that permeability can be tested subsequent to removal from the impactor. 相似文献
80.
The purpose of this study was to evaluate the hypothesis that spacer devices have limited effect on the in vitro fine particle
dose emitted from solution metered dose inhalers containing different proportions of HFA134a [1,1,1,2-tetrafluoroethane] propellant.
Two solution formulations (80% and 97.5% wt/wt HFA134a) were tested across the actuator alone, actuator plus Aerochamber,
and Ace holding chamber. Particle size distributions were determined using laser diffraction (LD) and cascade impaction (CI).
Multimodal particle size distributions were identified using LD. CI analyses were characterized by a major mode located at
≈0.5 μm. The fine particle dose emitted from the inhaler spacer combinations containing 97.5% HFA134a was independent of the
device setup used. Fine particle doses were influenced by spacer setup in 80% HFA134a formulations, indicating different plume
dynamics of low vapor pressure formulations. Sampling inlet deposition was approximately O when spacer devices were used with
either formulation. When spacers were not used, sampling inlet deposition was increased significantly. However, inlet deposition
with the 97.5% HFA134a formulation was significantly less than that of the 80% HFA134a formulation (≈25% of emitted dose compared
with 69% respectively). Thus, high propellant concentration formulations appear to have more robust in vitro performance.
This is particularly important given the preponderance of poor patient compliance that is associated with spacer use. High
propellant concentrations had the advantage of fine particle doses that were independent of the device setup and significantly
lowered sampling inlet deposition when no spacer was used. 相似文献