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941.
Jenifer L. Smith Kassandra I. Rossiter Christopher M. Semko Ying-Zi Xu David A. Quincy Jacek Jagodzinski Michael S. Dappen Andrei W. Konradi Christopher Vandevert Caroline Garrido Wenxian Mao F. Bong San Pablo Brian Wipke Lilibeth Dofiles Angie Wadsworth Eric Peterson Carlos Lorenzana Stellanie Simmonds Ted A. Yednock 《Bioorganic & medicinal chemistry letters》2013,23(14):4117-4119
Mitsunobu reactions were employed to link t-butyl esters of α4 integrin inhibitors at each of the termini of a three-arm, 40 kDa, branched PEG. Cleavage of the t-butyl esters using HCO2H provided easily isolated PEG derivatives, which are potent α4 integrin inhibitors, and which achieve sustained levels and bioactivity in vivo, following subcutaneous administration to rats. 相似文献
942.
Volume-activated chloride channels have been studied by us extensively in human nasopharyngeal carcinoma cells. However, the
chloride channels in the counterpart of the carcinoma cells have not been investigated. In this study, volume-activated chloride
currents (Icl,vol) were characterized in normal fetal human nasopharyngeal epithelial cells using the whole-cell patch-clamp technique. Under
isotonic conditions, nasopharyngeal epithelial cells displayed only a weak background current. Exposure to 47% hypotonic solution
activated a volume-sensitive current. The reversal potential of the current was close to the calculated equilibrium potential
for Cl−. The peak values of the hypotonicity-activated current at +80 mV ranged from 0.82 to 2.71 nA in 23 cells. Further analysis
indicated that the density of the hypotonicity-activated current in most cells (18/23) was smaller than 60 pA/pF. Only five
cells presented a current larger than 60 pA/pF. The hypotonicity-activated current was independent of the exogenous ATP. Chloride
channel inhibitors ATP, tamoxifen and 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), inhibited the current dramatically.
The anion permeability of the hypotonicity-activated chloride channels was I− > Br− > Cl− > gluconate. Unexpectedly, in isotonic conditions, ATP (10 mM) activated an inward-rectified current, which had not been
observed in the nasopharyngeal carcinoma cells. These results suggest that, under hypotonic challenges, fetal human nasopharyngeal
epithelial cells can produce Icl,vol, which might be involved in cell volume regulation. 相似文献
943.
Li J Fici GJ Mao CA Myers RL Shuang R Donoho GP Pauley AM Himes CS Qin W Kola I Merchant KM Nye JS 《The Journal of biological chemistry》2003,278(35):33445-33449
Nicastrin is a component of the gamma-secretase complex that has been shown to adhere to presenilin-1 (PS1), Notch, and APP. Here we demonstrate that Nicastrin-deficient mice showed a phenotype that is indistinguishable from PS1/PS2 double knock-out mice, whereas heterozygotes were healthy and viable. Fibroblasts derived from Nicastrin-deficient embryos were unable to generate amyloid beta-peptide and failed to release the intracellular domain of APP- or Notch1-Gal4-VP16 fusion proteins. Additionally, C- and N-terminal fragments of PS1 and the C-terminal fragments of PS2 were not detectable in Nicastrin-null fibroblasts, whereas full-length PS1 accumulated in null fibroblasts, indicating that Nicastrin is required for the endoproteolytic processing of presenilins. Interestingly, cells derived from Nicastrin heterozygotes produced relatively higher levels of amyloid beta-peptide whether the source was endogenous mouse or transfected human APP. These data demonstrate that Nicastrin is essential for the gamma-secretase cleavage of APP and Notch in mammalian cells and that Nicastrin has both positive and negative functions in the regulation of gamma-secretase activity. 相似文献
944.
945.
946.
Luoyu Wu Zhili Yuan Pengwei Wang Xuewei Mao Mingguo Zhou Yiping Hou 《Molecular Plant Pathology》2022,23(4):489-502
Fusarium graminearum, as the causal agent of Fusarium head blight (FHB), not only causes yield loss, but also contaminates the quality of wheat by producing mycotoxins, such as deoxynivalenol (DON). The plasma membrane H+-ATPases play important roles in many growth stages in plants and yeasts, but their functions and regulation in phytopathogenic fungi remain largely unknown. Here we characterized two plasma membrane H+-ATPases: FgPMA1 and FgPMA2 in F. graminearum. The FgPMA1 deletion mutant (∆FgPMA1), but not FgPMA2 deletion mutant (∆FgPMA2), was impaired in vegetative growth, pathogenicity, and sexual and asexual development. FgPMA1 was localized to the plasma membrane, and ∆FgPMA1 displayed reduced integrity of plasma membrane. ∆FgPMA1 not only impaired the formation of the toxisome, which is a compartment where DON is produced, but also suppressed the expression level of DON biosynthetic enzymes, decreased DON production, and decreased the amount of mycelial invasion, leading to impaired pathogenicity by exclusively developing disease on inoculation sites of wheat ears and coleoptiles. ∆FgPMA1 exhibited decreased sensitivity to some osmotic stresses, a cell wall-damaging agent (Congo red), a cell membrane-damaging agent (sodium dodecyl sulphate), and heat shock stress. FgMyo-5 is the target of phenamacril used for controlling FHB. We found FgPMA1 interacted with FgMyo-5, and ∆FgPMA1 showed an increased expression level of FgMyo-5, resulting in increased sensitivity to phenamacril, but not to other fungicides. Furthermore, co-immunoprecipitation confirmed that FgPMA1, FgMyo-5, and FgBmh2 (a 14-3-3 protein) form a complex to regulate the sensitivity to phenamacril and biological functions. Collectively, this study identified a novel regulating mechanism of FgPMA1 in pathogenicity and phenamacril sensitivity of F. graminearum. 相似文献
947.
Sebastian F. Barreto-Ortiz Shuming Zhang Matthew Davenport Jamie Fradkin Brian Ginn Hai-Quan Mao Sharon Gerecht 《PloS one》2013,8(11)
In microvascular vessels, endothelial cells are aligned longitudinally whereas several components of the extracellular matrix (ECM) are organized circumferentially. While current three-dimensional (3D) in vitro models for microvasculature have allowed the study of ECM-regulated tubulogenesis, they have limited control over topographical cues presented by the ECM and impart a barrier for the high-resolution and dynamic study of multicellular and extracellular organization. Here we exploit a 3D fibrin microfiber scaffold to develop a novel in vitro model of the microvasculature that recapitulates endothelial alignment and ECM deposition in a setting that also allows the sequential co-culture of mural cells. We show that the microfibers'' nanotopography induces longitudinal adhesion and alignment of endothelial colony-forming cells (ECFCs), and that these deposit circumferentially organized ECM. We found that ECM wrapping on the microfibers is independent of ECFCs'' actin and microtubule organization, but it is dependent on the curvature of the microfiber. Microfibers with smaller diameters (100–400 µm) guided circumferential ECM deposition, whereas microfibers with larger diameters (450 µm) failed to support wrapping ECM. Finally, we demonstrate that vascular smooth muscle cells attached on ECFC-seeded microfibers, depositing collagen I and elastin. Collectively, we establish a novel in vitro model for the sequential control and study of microvasculature development and reveal the unprecedented role of the endothelium in organized ECM deposition regulated by the microfiber curvature. 相似文献
948.
949.
盆栽非洲菊基因枪介导法转化体系的建立 总被引:3,自引:0,他引:3
以非洲菊盆栽品种为材料,研究了BA和NAA不同浓度组合对不定芽诱导增殖的影响;基因枪介导法转化的不同轰击距离对转化率影响。结果表明:1.5mg/LBA的培养基上增殖倍数最高,高达8.96倍;9cm的目标轰击距离转化效率最高,达到10.9%。建立了非洲菊盆栽品种的再生和转基因体系,为非洲菊基因工程育种打下基础。 相似文献
950.
Andrej Anokhin Ortrud Steinlein Christine Fischer Yiping Mao Peter Vogt Edda Schalt Friedrich Vogel 《Human genetics》1992,90(1-2):99-112
Summary The studied phenotype, the low-voltage electroencephalogram (LVEEG), is characterized by the absence of an alpha rhythm from the resting EEG. In previous studies, evidence was found for a simple autosomal-dominant mode of inheritance of the LVEEG. Such a polymorphism in brain function can be used as a research model for the stepwise elucidation of the molecular mechanism involved in those aspects of neuronal activity that are reflected in the EEG. Linkage with the variable number of tandem repeats (VNTR) marker CMM6 (D20S19) and localization of an LVEEG (EEGV1) gene on 20q have previously been reported, and genetic heterogeneity has been demonstrated. This latter result has been corroborated by studing new marker (MS214). The phenotype of the LVEEG is described here in greater detail. Its main characteristic is the absence of rhythmic alpha activity, especially in occipital leads, whereas other wave forms such as beta or theta waves may be present. Analysis of 17 new families (some of them large), together with 60 previously described nuclear families, supports the genetic hypothesis of an autosomal-dominant mode of inheritance. Problems connected with the analysis of linkage heterogeneity, exclusion mapping, and the study of multipoint linkage are discussed. A possible explanation of the localization of LVEEG in the close vicinity of another gene influencing synchronization of the normal EEG, the gene for benign neonatal epilepsie, is given. 相似文献