首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   41035篇
  免费   3290篇
  国内免费   3717篇
  48042篇
  2024年   116篇
  2023年   525篇
  2022年   1214篇
  2021年   1919篇
  2020年   1380篇
  2019年   1791篇
  2018年   1673篇
  2017年   1306篇
  2016年   1746篇
  2015年   2572篇
  2014年   3057篇
  2013年   3236篇
  2012年   3769篇
  2011年   3351篇
  2010年   2190篇
  2009年   1871篇
  2008年   2263篇
  2007年   1936篇
  2006年   1762篇
  2005年   1521篇
  2004年   1306篇
  2003年   1205篇
  2002年   1009篇
  2001年   812篇
  2000年   602篇
  1999年   591篇
  1998年   382篇
  1997年   364篇
  1996年   319篇
  1995年   280篇
  1994年   284篇
  1993年   184篇
  1992年   251篇
  1991年   222篇
  1990年   153篇
  1989年   125篇
  1988年   84篇
  1987年   118篇
  1986年   88篇
  1985年   72篇
  1984年   59篇
  1983年   44篇
  1982年   39篇
  1981年   26篇
  1980年   23篇
  1979年   25篇
  1978年   17篇
  1975年   21篇
  1974年   18篇
  1972年   17篇
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
151.
The effect of Haemonchus contortus galectin peptides rHco-gal-m/f to induce apoptosis in the peripheral blood lymphocytes (PBLCs) of goats was investigated. Analysis of apoptosis was carried out with agarose gel electrophoresis, flow cytometry and transmission electron microscopy. The results indicated that there were visible apoptosis bodies and typical DNA ladders by genomic DNA fragmentation. The quantitative analysis of apoptosis by flow cytometry indicated that rHco-gal-m/f peptides induced apoptosis was time and dose dependent. Ultrastructural studies of the PBLCs revealed that a large number of apoptotic cells were present in galectin-treated cells, which had the typical morphologic changes of apoptosis such as reduction of the cytoplasmic volume, loss of cell surface microvilli, chromatin condensation and fragmentation of the apoptotic cells into small apoptotic bodies.  相似文献   
152.
The cyclic peptide, cRGDf[N(me)]V, binds to the α v β 3 integrin and can disrupt binding of the integrin to its natural ligands in the extracellular matrix. In this work, the ability of a water-soluble, fluorescently labeled variant of the RGD-containing peptide (cRGDfK-488) to bind to integrins on human umbilical vascular endothelial cells (HUVEC) and subsequently undergo endocytosis was characterized. This information was compared to the binding and uptake properties of an α v β 3 integrin-specific monoclonal antibody, LM609X. The specificity of the RGD-containing peptide is assessed by comparison with control peptide that does not bind to the α v β 3 integrin, cRADfK-488. Using a high purity construct, it is shown that the RGD ligand exhibits dissociation constants in the micromolar range whereas LM609X exhibits dissociation constants in the nanomolar range. However, the RGD ligand showed greater uptake following incubation at temperatures which permit endocytosis. A 7.4-fold increase in uptake of the RGD peptide was observed following a 1 h incubation with HUVEC at 37°C (an endocytosis permissive temperature), as compared to that at 4°C (an endocytosis prohibitive temperature). In contrast, only a 1.9-fold increase in cell-associated fluorescence was observed for similar incubations with LM609X. Results from fluorescence microscopy supports the notion that the RGD peptide is rapidly endocytosed at 37°C as compared to LM609X. These results are discussed with regard to previous work indicating that RGD ligands enter cells by integrin-independent pathways. These studies provide well-controlled measures of how RGD ligands stimulate endocytosis. This may be of considerable interest for intracellular delivery of ligand-associated drugs in anti-angiogenic applications.  相似文献   
153.
处于对数生长期的光合细菌球形红假单胞菌(Rhodopseudomonassphaeroides)、沼泽红假单胞菌(Rhodopseudomonaspalustris)、嗜酸红假单胞菌(Rhodopseudomdnasacidophila)、深红红螺菌(Rhodospirarubrum)、万尼氏红微菌(Rhodomocrobiumvannielii),经溶菌酶(3mg/L)处理50min后,获得了它们的菌体形成的原生质体,其再生率分别为80%、71%、82%、61%、74%.取等量的亲本菌株在35%的PEG(MW6000)诱导下两两融合5min,共10种组合.其融合率为球×沼2.5×10-4、球×嗜2.1×10-4、球×深2.0×10-4、球×万2.1×10-4、沼×嗜2.8×10-4、沼×深2.4×10-4、沼×万2.6×10-4、嗜×深2.0×10-4、嗜×万2.3×10-4、深×万2.4×10-4.经影印法鉴定:形成的融合子可以分别生长于以相应的有机物为唯一碳源的培养基上,所有融合子体积均相当于两亲本株体积之和,融合子菌落形态特征介于两亲本株之间.从中随机挑选100个融合子,以辣椒苗作为靶标植物,从上述融合子中筛选到了1株具有显著促进作物生长、提高抗病性的融合子.  相似文献   
154.
155.
Cellulases can penetrate into the fiber, causing tensile strength loss of the cellulosic fibers or fabrics. To minimize the tensile strength loss, we have immobilized cellulases on Eudragit S‐100. The characteristics of covalent Eudragit cellulase were evaluated using gel filtration analysis and UV spectra. Gel filtration analysis revealed that the cellulases were covalently bound to the polymer. Covalent Eudragit cellulase was loaded with the enzyme of about 40% and had a relative activity about 80% at a Eudragit S‐100 concentration of 15 g/L. When cellulase is bound to the polymer, the solubility profile becomes similar to the one of Eudragit. In addition, the effects of the enzyme on the cotton yarns and fabric using cellulases have been investigated. Native and immobilized cellulases caused improvements in whiteness and wrinkle recovery angle of the fabric in comparison to the control samples. The bending stiffness results show that native and immobilized cellulase treated cotton fabric has an improved softness than the control samples. It was found that using the immobilized cellulase reduced the weight and tensile strength, because the hydrolytic attack is only limited to the surfaces of cotton fibers.  相似文献   
156.
157.
本文对赤(瓜包)属(Thladiantha Bunge)、白兼果属(Baijiana A.M.Lu et J.Q.Li)和苦瓜属(Momordica L.)共11种植物叶片中脉进行了比较解剖学研究。除苦瓜属一种外,其余10种的叶片中脉解剖学资料均为首次报道。分析结果表明:叶片中脉维管束的数目以及排列方式具有分类学意义,而种间和种内维管束数目的减少,在一定程度上反映出植物迁移和演化的方向。  相似文献   
158.
Z Wang  Y Zhou  X Hu  W Chen  X Lin  L Sun  X Xu  W Hong  T Wang 《Cell death & disease》2015,6(10):e1923
RILP (Rab7-interacting lysosomal protein) is a key regulator for late endosomal/lysosomal trafficking, and probably a tumor suppressor in prostate cancer. However, the role of RILP in other cancers and the underlying mechanism for RILP in regulating the invasion of cancer cells remain to be investigated. In this study, we showed that overexpression of RILP in breast cancer cells inhibits the migration and invasion, whereas the depletion of RILP by RNAi-mediated knockdown promotes the migration and invasion. We identified RalGDS (Ral guanine nucleotide dissociation stimulator) as a novel interacting partner for RILP, and truncation analysis revealed the N-terminal region of RILP is responsible for interacting with the guanine nucleotide exchange factor (GEF) domain of RalGDS. Immunofluorescence microscopy revealed that RalGDS can be recruited to the late endosomal compartments by RILP. Further investigations indicated that the overexpression of RILP inhibits the activity of RalA, a downstream target of RalGDS. Our data suggest that RILP suppresses the invasion of breast cancer cells by interacting with RalGDS to inhibit its GEF activity for RalA.Diverse alternations of oncogenic factors can either activate or inactivate signaling pathways involved in cell proliferation, migration and apoptosis that are intimately associated with cancer development.1, 2, 3 Recent studies suggest that the derailed membrane trafficking is also closely related to cancer development. Activation or attenuation of signal transduction is usually linked to membrane trafficking. The recycling and degradation of surface receptors, such as EGFR, will influence downstream signaling pathways.4, 5 Therefore, the cross-talk between membrane trafficking and signaling pathway could be the novel mechanism associated with cancer development.Alternations of the membrane trafficking machineries are established as the causes for some cancers. For examples, Rab25 is overexpressed in breast and ovary caners,6 and recent investigations suggest that Rab25 is also related to other cancers.7, 8, 9 Arf6 is a vital regulator for the invasive activity of breast cancer cells.10 Disordered membrane trafficking is emerging as an important property during tumorigenesis, thus the membrane trafficking machineries are potential therapeutic targets for cancer treatment.Rab small GTPases are considered as the master regulators for membrane trafficking.11 The interactions between Rab proteins and their downstream effectors are involved in various steps of vesicle trafficking such as tethering and fusion. Aberrant activities of Rab proteins are closely related to some cancers.12, 13, 14, 15 Some Rab proteins mediate the trafficking of cargos, especially membrane proteins on the plasma membrane, such as integrin and E-cadherin. Their aberrant trafficking is proposed to be the underlying mechanism for the functional regulation of Rab protein in cancer cells.16, 17Rab7, together with its downstream effector RILP (Rab7-interacting lysosomal protein), are the key regulators for late endosomal/lysosomal trafficking. RILP interacts with activated GTP-bound Rab7 through its carboxylic terminal region, whereas interacting with dynein/dynactin complex is mediated through its amino region, driving late endosomal/lysosomal trafficking, especially lysosomal positioning.18, 19 Rab7 has been demonstrated to be an important factor for cell growth and survival.20, 21 Recently, Steffan et al.22 found that RILP suppresses the invasion of prostate cancer cells through inhibiting the anterograde trafficking of lysosomes.23 Whether the potential role of Rab7-RILP in cell migration/invasion is also implicated in other cancers is of interest to investigate and the underlying molecular mechanism is yet to be defined.In this study, we found that RILP suppresses the proliferation, migration and invasion of breast cancer cells. We also identified (Ral guanine nucleotide dissociation stimulator (RalGDS) as a novel interacting partner for RILP. The interaction of RILP with RalGDS modulates the activity of RalA. Our results suggest that RILP suppresses the invasion of breast cancer cells by modulating the activity of RalA through interaction with RalGDS.  相似文献   
159.
邴健  白逢彦 《菌物学报》2018,37(11):1441-1453
近年来的基因组学研究结果已证实拉格啤酒酵母Saccharomyces pastorianus是一个由艾尔啤酒酵母S. cerevisiae和真贝氏酿酒酵母S. eubayanus杂交而成的杂交种,并可根据地域传承和染色体倍性分为两个株系,即I型/Saaz系和II型/Frohberg系。前者主要为异源3倍体,后者则主要为异源4倍体。为了探讨中国啤酒酿造酵母菌的物种和菌系归属,我们根据拉格啤酒酵母及其两个菌系的基因组特性,制定了一套基于IntFR片段种特异性扩增和ITS-RFLP分析的精确但简便易行的拉格啤酒酵母菌物种和株系鉴定新方法,并以酿酒酵母属内相关种的模式或权威菌株和部分酒精及面包酵母为参照,对保藏于中国普通微生物菌种保藏中心(CGMCC)的41株啤酒酿造酵母菌进行了重新鉴定和分型。这些菌株除1株原定名为贝氏酿酒酵母S. bayanus外,其余菌株的原定名均为S. cerevisiae。研究结果确认了S. bayanus菌株鉴定的正确性,但在其余的40株啤酒酵母菌株中,21株属于S. cerevisiae,1株属于葡萄汁酿酒酵母S. uvarum,18株属于S. pastorianus。菌系鉴定和流式细胞测定结果显示在确认的S. pastorianus菌株中,1株为I型/Saaz系,3倍体;17株为II型/Frohberg系,其中9株为4倍体,两株为3倍体,5株介于3倍至4倍体之间。啤酒酵母物种和株系的确认对优化发酵工艺和菌种选育及遗传改造等具有重要意义。  相似文献   
160.
本文记述采自江西省修水县的管蛛属蜘蛛一新种:中华管蛛Trachelassinensissp.nov.。该种与日本管蛛T.japonicaBoes.etStr.,1906在体型,体色及腹部背面的斑纹上非常相似,但该种的身体明显大于后者,两者外生殖器存在明显的差异。  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号