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971.
Rick?K. Huang Ulrich Baxa Gudrun Aldrian Abdullah?B. Ahmed Joseph?S. Wall Naoko Mizuno Oleg Antzutkin Alasdair?C. Steven Andrey?V. Kajava 《Biophysical journal》2014,106(10):2134-2142
The established correlation between neurodegenerative disorders and intracerebral deposition of polyglutamine aggregates motivates attempts to better understand their fibrillar structure. We designed polyglutamines with a few lysines inserted to overcome the hindrance of extreme insolubility and two D-lysines to limit the lengths of β-strands. One is 33 amino acids long (PolyQKd-33) and the other has one fewer glutamine (PolyQKd-32). Both form well-dispersed fibrils suitable for analysis by electron microscopy. Electron diffraction confirmed cross-β structures in both fibrils. Remarkably, the deletion of just one glutamine residue from the middle of the peptide leads to substantially different amyloid structures. PolyQKd-32 fibrils are consistently 10–20% wider than PolyQKd-33, as measured by negative staining, cryo-electron microscopy, and scanning transmission electron microscopy. Scanning transmission electron microscopy analysis revealed that the PolyQKd-32 fibrils have 50% higher mass-per-length than PolyQKd-33. This distinction can be explained by a superpleated β-structure model for PolyQKd-33 and a model with two β-solenoid protofibrils for PolyQKd-32. These data provide evidence for β-arch-containing structures in polyglutamine fibrils and open future possibilities for structure-based drug design. 相似文献
972.
Jain S Mythily S Ahmed RS Arora VK Banerjee BD 《Indian journal of biochemistry & biophysics》2010,47(6):388-392
The effect of triazophos (O, O-diethyl O-1-phenyl-1 H-1, 2, 4-triazol-3-yl phosphorothioate), a widely used insecticide was studied on the induction of oxidative stress and histological alterations at sub-chronic doses in male albino rats. Oral administration of triazophos at concentrations of 1.64, 3.2 and 8.2 mg/kg body wt for 30 days produced dose as well as time-dependent increase in the lipid peroxidation (determined by malondialdehyde levels) and glutathione-S-transferase (GST) activity in serum with aconcomitant decrease in ferric reducing ability of plasma (FRAP) and blood glutathione (GSH) content. Histopathological examination of liver of triazophos-treated rats showed significant and progressive degenerative changes as compared to control, which could be due to induction of oxidative stress. However, no significant histopathological changes were observed in spleen, kidney and brain at either dose of triazophos with respect to control. These results indicated that oral administration of triazophos was associated with enhanced lipid peroxidation and compromised antioxidant defence in rats in dose and time-dependent manner. Thus the present study demonstrated for the first time the role of oxidative stress as the important mechanism involved in the stimulation of hepatic histoarchitectural alterations at sub-chronic doses of triazophos in rats. 相似文献
973.
Mostafa A. Yehia Tarek S. El-Ammawi Khairia M. Al-Mazidi Mahmoud A. Abu El-Ela Hejab S. Al-Ajmi 《Mycopathologia》2010,169(4):241-246
Background
Fungal infections constitute a major health problem all over the world. Signs and symptoms induced by various dermatophytic infections are difficult to distinguish clinically from each other. So, characterization by in vitro culture is required for appropriate diagnosis and treatment as well as to study the epidemiological characteristics in a region. 相似文献974.
Jin Woo Park Sang Kyoon Kim Taslim Ahmed Al-Hilal Ok Cheol Jeon Hyun Tae Moon Youngro Byun 《Biotechnology and Bioprocess Engineering》2010,15(1):66-75
Advances in biotechnology, gene manipulation, and protein engineering for macromolecule drugs, such as insulin, parathyroid
hormone (PTH), calcitonin, human growth hormone, erythropoietin (EPO), and peptide YY (PYY) allow commercial production in
large scale for diverse therapeutic uses. Other macromolecules, such as mucopolysaccharide heparin, have expanded markets
through improvements in their pharmacokinetic and pharmacological effects. However, most products are available only as injectable
forms and are limited to patients with no alternative therapeutic choices. Orally available macromolecule formulations are
still unmet needs for improving patient compliance and expanding administration paradigms and indications. Oral delivery technologies
including carrier systems, absorption enhancers, protease inhibitors, and modification by conjugating transporter or receptor
recognition molecules have been developed and some are undergoing clinical studies. In this review, we discuss major obstacles
for oral absorption of macromolecule drugs and summarize recent strategies to overcome the huddles related to enhancing intestinal
permeation. 相似文献
975.
Ahmed Chahdi 《Biochemical and biophysical research communications》2010,391(3):1330-1335
Endothelin-1 (ET-1) is a potent mitogen that transmits signals through its cognate G protein-coupled receptors to stimulate extracellular signal-regulated kinase Erk1/2. Endothelin-1 receptors (ET-Rs) are known to interact with caveolin-1 and co-localize in caveolae which integrate different receptor and signaling proteins. We have recently shown that β1Pix binds specifically to ET-Rs. Here, we show that β1Pix binding to caveolin-1 is dependent on heterotrimeric G proteins activation state. β1Pix interaction with different G proteins is increased in the presence of the G protein activator AMF. Moreover, extraction of cholesterol with methyl-β-cyclodextrin disrupts the binding of β1Pix to Gαq, Gα12 and phospho-Erk1/2 but not the binding of β1Pix to Gβ1. The disruption of β1Pix dimerization strongly reduced the binding of caveolin-1, Gαq and Gα12. Constitutively active mutants of Gαq and Gα12 increased Cdc42 activation when co-expressed with β1Pix but not in the presence of β1Pix dimerization deficient mutant β1PixΔ (602-611). ET-1 stimulation increased the binding of phosphorylated Erk1/2 to β1Pix but not to β1PixΔ (602-611). RGS3 decreased ET-1-induced Cdc42 activation. These results strongly suggest that the activation of ET-Rs leads to the compartmentalization and the binding of Gαq to β1Pix in caveolae, where dimeric β1Pix acts as platform to facilitate the binding and the activation of Erk1/2. 相似文献
976.
In this paper we consider the fractional order model with two immune effectors interacting with two strain antigen. The systems
may explain the recurrence of some diseases e.g. tuberculosis (TB). The stability of equilibrium points are studied. Numerical
solutions of this model are given. Using integer order system the system oscillates. Using fractional order system the system
converges to a stable internal equilibrium. Ulam-Hyers stability of the system has been studied. 相似文献
977.
To fill in some of the gaps in our knowledge of Schizogony of Haemoproteus columbae Kruse, transmission experiments involving inoculation into pigeons (Columba livia Gmelin) of sporozonites from salivary glands of the hippoboscid fly Pseudolynchia canariensis (Macquart) were carried out. We were unable to detect prepatent schizonts or to observe schizogonic development when infection became chronic. Schizonts were mainly confined to lung tissue. Observations of parapatent schizonts were made in smears and tissue sections. A variety of forms was found. Cytomeres were rarely encountered. Two types of morphologically distinct merozoites were seen. One type was twice as large as large as the other and was thought to repeat the process of schizogony several times before invading erythrocytes. Schizonts with cytoplasmic clefts were not common in our material due to the fixatives used (Bouin's and Carnoy's). Merozoites were occasionally observed inside monocytes, probably being phagocytosed. 相似文献
978.
979.
Seyedeh Sara Shafiei Mehran Solati-Hashjin Ali Samadikuchaksaraei Reza Kalantarinejad Mitra Asadi-Eydivand Noor Azuan Abu Osman 《PloS one》2015,10(8)
In recent years, nanotechnology in merging with biotechnology has been employed in the area of cancer management to overcome the challenges of chemopreventive strategies in order to gain promising results. Since most biological processes occur in nano scale, nanoparticles can act as carriers of certain drugs or agents to deliver it to specific cells or targets. In this study, we intercalated Epigallocatechin-3-Gallate (EGCG), the most abundant polyphenol in green tea, into Ca/Al-NO3 Layered double hydroxide (LDH) nanoparticles, and evaluated its efficacy compared to EGCG alone on PC3 cell line. The EGCG loaded LDH nanohybrids were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy (TEM) and nanosizer analyses. The anticancer activity of the EGCG-loaded LDH was investigated in prostate cancer cell line (PC3) while the release behavior of EGCG from LDH was observed at pH 7.45 and 4.25. Besides enhancing of apoptotic activity of EGCG, the results showed that intercalation of EGCG into LDH can improve the anti- tumor activity of EGCG over 5-fold dose advantages in in-vitro system. Subsequently, the in-vitro release data showed that EGCG-loaded LDH had longer release duration compared to physical mixture, and the mechanism of diffusion through the particle was rate-limiting step. Acidic attack was responsible for faster release of EGCG molecules from LDH at pH of 4.25 compared to pH of 7.4. The results showed that Ca/Al-LDH nanoparticles could be considered as an effective inorganic host matrix for the delivery of EGCG to PC3 cells with controlled release properties. 相似文献
980.
Hazel J. Hunt Nicholas C. Ray George Hynd Jon Sutton Mohammed Sajad Elizabeth O’Connor Shahadat Ahmed Peter Lockey Steve Daly Gerry Buckley Robin D. Clark Robert Roe Christine Blasey Joe Belanoff 《Bioorganic & medicinal chemistry letters》2012,22(24):7376-7380
We report the optimization of a series of non-steroidal GR antagonists that led to the identification of compound 7. This compound is efficacious when dosed orally in an olanzapine-induced weight gain model in rats. 相似文献