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81.
Synthesis, conformational studies and biological activity of N(alpha)-mono-biotinylated rat relaxin.
M N Mathieu J D Wade B Catimel C P Bond E C Nice R J Summers L Otvos G W Tregear 《The journal of peptide research》2001,57(5):374-382
Biotin-avidin immobilization can be a useful tool in structure-function studies of hormone receptors. A crucial step is the preparation of a specifically biotinylated hormone that is able to bind to its receptor while leaving the biotin group free for interaction with avidin. The receptor for relaxin, an ovarian peptidic hormone produced during pregnancy, has not yet been isolated. We therefore undertook to prepare a specifically monobiotinylated rat relaxin for use in ligand-searching strategies. Rat relaxin is a convenient analogue because reliable bioassays exist, thus allowing assessment of the effect of N-biotinylation on bioactivity. To help improve the yield of the two-chain, three-disulfide bond rat relaxin, 2-hydroxy-4-methoxybenzyl (Hmb) backbone protection was used during the solid-phase assembly of the B-chain to help prevent any possible chain aggregation. As a final step, while the protected peptide was still on the resin, the biotin label was introduced at the N-terminus of the B-chain using standard coupling protocols. The chain combination with the A-chain was accomplished in reasonable yield. Secondary structural measurements demonstrated that the biotin caused the starting B-chain to adopt a more ordered conformation. The labelled synthetic relaxin exhibited similar circular dichroism spectra to native and synthetic single B-chain peptides. In addition, the biotinylated relaxin showed no significant difference in its chronotropic activity in the rat isolated heart assay compared with the native peptide. Biosensor studies showed that antibody recognition was retained upon attachment of the synthetic relaxin to the streptavidin-derivatized surface. 相似文献
82.
83.
An ATP-Sensitive K+ Current that Regulates Progression Through Early G1 Phase of the Cell Cycle in MCF-7 Human Breast Cancer Cells 总被引:4,自引:0,他引:4
Whole-cell recordings were used to identify in MCF-7 human breast cancer cells the ion current(s) required for progression
through G1 phase of the cell cycle. Macroscopic current-voltage curves were fitted by the sum of three currents, including
linear hyperpolarized, linear depolarized and outwardly rectifying currents. Both linear currents, but not the outwardly rectifying
current, were increased by 1 μm intracellular Ca2+ and blocked by 2 mm intracellular ATP. When tested at concentrations previously shown to inhibit proliferation by 50%, linogliride, glibenclamide
and quinidine inhibited the linear hyperpolarized current, and quinidine and linogliride inhibited the linear depolarized
current; none of these agents affected the outwardly rectifying current. In contrast, tetraethylammonium completely inhibited
the outwardly rectifying current, but did not inhibit either linear current. Changing the bath solution to symmetric K+ shifted the reversal potential of the linear hyperpolarized current from near the K+ equilibrium potential (−84 mV) to −4 mV. Arrest of the cell cycle in early G1 by quinidine was associated with significantly
smaller linear hyperpolarized currents, without a change in the linear depolarized or outwardly rectifying currents, but this
reduction was not observed with arrest by lovastatin at a site ≈6 hr later in G1. The linear hyperpolarized current was significantly
larger in ras-transformed than in untransformed cells. We conclude that the linear hyperpolarized current is an ATP-sensitive K+ current required for progression of MCF-7 cells through G1 phase.
Received: 22 January 1999/Revised: 11 May 1999 相似文献
84.
85.
CD44-deficient mice develop normally with changes in subpopulations and recirculation of lymphocyte subsets. 总被引:9,自引:0,他引:9
U Protin T Schweighoffer W Jochum F Hilberg 《Journal of immunology (Baltimore, Md. : 1950)》1999,163(9):4917-4923
Cell adhesion molecules are considered to be pivotal elements required for proper embryo development. The transmembrane glycoprotein CD44, which is expressed in numerous splice variants on the surface of many different cell types and tissues, has been suggested to be involved in several physiological processes such as cell-cell interactions, signal transduction, and lymphocyte homing and trafficking during embryogenesis and in the adult organism. Some splice variants are thought to play an important role in tumor progression. To investigate the physiological roles of CD44 in vivo, we abolished expression of all isoforms of CD44 in mice by targeted insertion of a lacZ/neo cassette into the reading frame of the leader peptide. CD44-deficient mice are viable without obvious developmental defects and show no overt abnormalities as adults. However, CD44-deficient lymphocytes exhibit impaired entry into the adult thymus, although lymphocyte development is apparently unaltered. Our data indicate that all splice variants of CD44 are dispensable for embryonic development and implicate a critical function for CD44 in lymphocyte recirculation. 相似文献
86.
We used water-soluble styryl pyridinium dyes that fluoresce at the membrane-water interface to study vesicle traffic in endothelial
cells. Cultured endothelial cells derived from bovine and human pulmonary microvessels were incubated in styryl probes, washed
to remove dye from the plasmalemmal outer face, and observed by digital fluorescence microscopy. Vesicles that derived from
plasmalemma by endocytosis were filled with the styryl dye. These vesicles were distributed throughout the cytosol as numerous
particles of heterogeneous diameter and brightness. Vesicle formation was activated 2-fold following addition of extracellular
albumin whereas a control protein, immunoglobulin G, had no effect. Dye uptake was abrogated by labeling at low temperatures
and inhibitors of phosphoinositide-3-kinase (PI 3-kinase). Tyrosine kinase inhibitors (genistein and herbimycin A) prevented
the albumin-induced vesicle formation. Cytochalasin B prevented vesicle redistribution indicating involvement of actin filaments
in translocation of endosomes away from sites of vesicle formation. Styryl dye was lost from cells by exocytosis as evident
by the disappearance of discrete fluorescent particles. N-ethylmaleimide and botulinum toxin types A and B caused cells to accumulate increased number of vesicles suggesting that exocytosis was regulated by NSF-dependent
SNARE mechanism. The results suggest that phosphoinositide metabolism regulates endocytosis in endothelial cells and that
extracellular albumin activates endocytosis by a mechanism involving tyrosine phosphorylation, whereas exocytosis is a distinct
process regulated by the SNARE machinery. The results support the hypothesis that albumin regulates its internalization and
release in vascular endothelial cells via activation of specific endocytic and exocytic pathways. 相似文献
87.
The retinoid receptors (RARs and RXRs) are mediators of the multiple effects of retinoic acid. Of these, the retinoic acid receptor beta2 (RARbeta2) has frequently been shown to be the principal mediator of the growth and tumor suppressive effects of retinoic acid; this gene is inactivated in many epithelial tumors and their derived cell lines. We have searched for genes that are regulated by this isoform and are potentially involved in tumor suppression. Using the Atlas human cDNA array I, we identified 27 genes (not counting RARbeta itself) that are regulated, directly or indirectly, by RARbeta2 when it is transfected into Calu-1, a lung tumor-derived line that does not normally express RARbeta. Several of the affected genes code for proteins whose functions would augment the process of apoptosis and/or the host's immune response. The latter group included ICAM-1 and MHC class I heavy chain, whose protein products play particularly important roles in the mounting of an effective anti-tumor response. We then confirmed by flow cytometry that the observed increases in message levels were reflected in increased cell surface protein levels for ICAM-1 and MHC class I in RARbeta2 transfectants of two RARbeta-deficient lines, Calu-1 and the epidermoid lung cancer-derived line SK-MES. Finally, we showed that RARbeta2 transfection of Calu-1 cells enhanced the heterologous CTL response in both the induction and the effector phases by up to threefold. These results support the hypothesis that down-regulation of these genes (and possibly others) in RARbeta-deficient tumor cells contributes to immune system evasion, and suggest a novel therapeutic approach for this disease. 相似文献
88.
Anti-inflammatory effects of sodium butyrate on human monocytes: potent inhibition of IL-12 and up-regulation of IL-10 production. 总被引:4,自引:0,他引:4
M D S?emann G A B?hmig C H Osterreicher H Burtscher O Parolini C Diakos J St?ckl W H H?rl G J Zlabinger 《FASEB journal》2000,14(15):2380-2382
Cytokines are critical in regulating unresponsiveness versus immunity towards enteric antigens derived from the intestinal flora and ingested food. There is increasing evidence that butyrate, a major metabolite of intestinal bacteria and crucial energy source for gut epithelial cells, also possesses anti-inflammatory properties. Its influence on cytokine production, however, is not established. Here, we report that butyrate strongly inhibits interleukin-12 (IL-12) production by suppression of both IL-12p35 and IL-12p40 mRNA accumulation, but massively enhances IL-10 secretion in Staphylococcus aureus cell-stimulated human monocytes. The effect of butyrate on IL-12 production was irreversible upon the addition of neutralizing antibodies to IL-10 or transforming growth factor b1 and of indomethacin. In anti-CD3-stimulated peripheral blood mononuclear cells, butyrate enhanced IL-10 and IL-4 secretion but reduced the release of IL-2 and interferon-g. The latter effect was in part a result of suppressed IL-12 production but also a result of inhibition of IL-12 receptor expression on T cells. These data demonstrate a novel anti-inflammatory property of butyrate that may have broad implications for the regulation of immune responses in vivo and could be exploited as new therapeutic approach in inflammatory conditions. 相似文献
89.
Origins of Life and Evolution of Biospheres - 相似文献