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991.
Mifeprlstone,a norethindrone, is the first synthetic effective steroid which canbind to the progesterone receptor with greater affinity than progesterone, but lacksthe agonistic effect. Its anti--progestin action results in the withdrawal of progesterone at cellular level to interrupt its biological action and can terminate early pregnancy['j. At present, the dose of mifepristone in combination with the analogue ofprostaglandin in terminating early pregnancy is 150 mg-- 200 mg and the complete… 相似文献
992.
ZHANG Xiang SUN Zhi-da SHENG Wei-xiong JIANG De-qi ZHU Yue-hua WANG Han-zheng JIN Li 《生殖与避孕(英文版)》2000,11(2)
Objective To provide the theoretical fundation for the further clinical application of mi fepristone and anordrin compound. Materials & Methods Ribonuclease protection assay was used for the detection and quantitation of estrogen and progesterone receptor mRNAs in human decidua from the termination of early pregnancy. Three groups, each of which had 6~8 cases, were studied. Results Compared to the normal control group, estrogen and progesterone receptor mRNAs increased significantly (P<0.05) in the mifepristone group, whereas the changes in the group administrated mifepristone compound which contains anordrin were not obvious. Conclusions The result suggests that with the similar clinical effect, mifepristone compound has less side effect on the patients, thus being more suitable for the anti-ear ly pregnancy drug. 相似文献
993.
In order to investigate the mechanism of progestin and antiprogestin in the regula tion of ovarian steroidogenesis, a dual-chamber culture system was prepared with the amnion membrane of human placenta. Isolated porcine granulosa and thecal cells from 4~6 mm-diameter follicles were grown on both sides of the amnion, respectively, and co-cultured with or without LNG and RU486. After 48 h incubation, the mRNAs of FSH receptor (FSH-R) and LH receptor (LH-R) of both cells were observed by in situ hybridization. The results showed that granulosa cells expressed both FSH-R mR NA and LH-R mRNA, while thecal cells expressed LH-R mRNA only. Under the stimulation of FSH, both LNG and RU486 increased FSH-R mRNA expression of granulosa cells. Under the stimulation of LH, LNG enhanced LH-R mRNA expres sion of thecal cells; while RU486 decreased its expression. When granulosa and thecal cells were exposed to FSH and LH both, the actions of LNG and RU486 in thecal cells showed the same result as that stimulated by LH alone. In granulosa cells LNG de creased LH-R mRNA expression, while RU486 increased its expression. These data suggest that: (1) granulosa cells expressed FSH-R mRNA significantly;(2) both the progestin and antiprogestin directly acted on the mRNA expression of gonadotropin re ceptors of ovarian cells, but effects were different; (3) the response of granulosa or thecal cells to the action of LNG and RU 486 was not the same. The mechanism needs to be further investigated. 相似文献
994.
One of the fundamental properties of a neuronal circuit is the map of its connections. The cellular and developmental processes that allow for the growth of axons and dendrites, selection of synaptic targets, and formation of functional synapses use neuronal surface receptors and their interactions with other surface receptors, secreted ligands, and matrix molecules. Spatiotemporal regulation of the expression of these receptors and cues allows for specificity in the developmental pathways that wire stereotyped circuits. The families of molecules controlling axon guidance and synapse formation are generally conserved across animals, with some important exceptions, which have consequences for neuronal connectivity. Here, we summarize the distribution of such molecules across multiple taxa, with a focus on model organisms, evolutionary processes that led to the multitude of such molecules, and functional consequences for the diversification or loss of these receptors. 相似文献
995.
Akitaka Yamasaki Kumiko Maruyama-Takahashi Kento Nishida Shogo Okazaki Kouki Okita Yasutoshi Akiyama Hideaki Suzuki Yuichi Endo Kazue Masuko Takashi Masuko Yoshihisa Tomioka 《Genes to cells : devoted to molecular & cellular mechanisms》2023,28(5):374-382
Human epidermal growth factor receptor (HER) family proteins are currently major targets of therapeutic monoclonal antibodies against various epithelial cancers. However, the resistance of cancer cells to HER family-targeted therapies, which may be caused by cancer heterogeneity and persistent HER phosphorylation, often reduces overall therapeutic effects. We herein showed that a newly discovered molecular complex between CD98 and HER2 affected HER function and cancer cell growth. The immunoprecipitation of the HER2 or HER3 protein from lysates of SKBR3 breast cancer (BrCa) cells revealed the HER2-CD98 or HER3-CD98 complex. The knockdown of CD98 by small interfering RNAs inhibited the phosphorylation of HER2 in SKBR3 cells. A bispecific antibody (BsAb) that recognized the HER2 and CD98 proteins was constructed from a humanized anti-HER2 (SER4) IgG and an anti-CD98 (HBJ127) single chain variable fragment, and this BsAb significantly inhibited the cell growth of SKBR3 cells. Prior to the inhibition of AKT phosphorylation, BsAb inhibited the phosphorylation of HER2, however, significant inhibition of HER2 phosphorylation was not observed in anti-HER2 pertuzumab, trastuzumab, SER4 or anti-CD98 HBJ127 in SKBR3 cells. The dual targeting of HER2 and CD98 has potential as a new therapeutic strategy for BrCa. 相似文献
996.
Karen B Jourdan Timothy W Evans Nicholas P Curzen Jane A Mitchell 《British journal of pharmacology》1997,120(7):1280-1285
- 8-Iso prostaglandin F2α (8-iso PGF2α) is one of a series of prostanoids formed independently of the cyclo-oxygenase pathway. It has been shown to be upregulated in many conditions of oxidant stress where its formation is induced by free radical-catalysed actions on arachidonic acid. As 8-iso PGF2α is formed in vivo in diseases in which oxidant stress is high such as septic shock, we have assessed the relative potency and efficacy of this compound in pulmonary arteries from control and lipopolysaccharide (LPS)-treated rats.
- Several studies have characterized the contractile actions of 8-iso PGF2α on various smooth muscle preparations, but its potential dilator actions have not been addressed. Thus these studies examined both the contractile and dilator actions of 8-iso PGF2α in rat pulmonary artery rings. The thromboxane mimetic U46619, PGE2 sodium nitroprusside (SNP) and acetyl choline (ACh) were used for comparison. Each prostanoid had to be dissolved in ethanol to a maximum concentration of 1×10−2 M. At high concentrations, ethanol directly contracted pulmonary vessels. We were therefore limited by the actions of the vehicle such that we were unable to add prostanoids at concentrations higher than 1×10−4 M. In some cases this meant that maximum responses were not achieved and in these cases the Emax and pD2 values are apparent estimates.
- The following rank order of potency was obtained from contractile studies; U46619>8-iso PGF2α>PGE2, each prostanoid producing concentration-dependent contractions (10−103×10−4 M, 10−910−4 M, 10−810−4 M, respectively). As has been shown previously for other smooth muscle preparations, the thromboxane receptor (TP) antagonist ICI 192605, (1×10−6, 1×10−5 and 1×10−4 M), inhibited the contractions of 8-iso PGF2α in a concentration-dependent fashion.
- The nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 1×10−4 M), enhanced the contractile function of both 8-iso PGF2α and PGE2, but had no effect on that caused by U46619. Similarly, L-NAME inhibited the dilator function of all agents tested except the exogenous nitric oxide (NO) donor SNP, indicating that PGE2 and 8-iso PGF2α like ACh, act through the release of NO. The specificity of the effects of L-NAME were confirmed in studies with the inactive enantiomer D-NAME (1×10−4 M), which did not affect the contractile or the dilator actions of 8-iso PGF2α. Furthermore, ICI 192605 enhanced the dilator actions of 8-iso PGF2α, suggesting that the dilator component of 8-iso PGF2α was achieved via activation of a non-TP receptor.
- Isoprostanes may modulate vascular tone by a direct action on TP receptors to cause contraction and via a distinct receptor leading to the release of NO to cause dilatation.
997.
Masatsugu Nakamura Keiko Ofuji Tai-ichiro Chikama Teruo Nishida 《British journal of pharmacology》1997,120(4):547-552
- We have previously shown that substance P (SP) and insulin-like growth factor-1 (IGF-1) act synergistically to enhance the migration of rabbit corneal epithelial cells in an organ culture model. The present study was designed to identify the epithelial cell SP receptor that participates in this synergistic effect.
- Rabbit corneal blocks were incubated for 24 h, then the length of the path of epithelial migration was measured. Reagents tried in the TC-199 culture medium, in the presence or absence of IGF-1, were: SP, agonists of tachykinin receptors NK1, NK2 or NK3 and antagonists of tachykinin receptors NK1 or NK2.
- The binding characteristics of SP receptors were examined in rabbit cultured corneal epithelial cells by binding assays with [125I]-SP in the presence or absence of excess unlabelled SP or ligands of NK1, NK2 or NK3 receptors.
- As was demonstrated previously, SP and IGF-1 stimulated epithelial migration when they were added to the culture medium together, but individually they had no effect. NK1 agonists had the same synergistic effect with IGF-1 as did SP, but the NK2 and NK3 agonists did not. Furthermore, the NK1 antagonist abolished the synergistic effect of SP and IGF-1, but the NK2 antagonist had no effect.
- SP bound specifically to rabbit cultured corneal epithelial cells. The binding affinity was 0.44 nM and there were 2.43×104 binding sites per cell. The NK1 ligand competed, in a dose-dependent fashion, with the binding of SP to corneal epithelial cells, but neither the NK2 nor NK3 ligand affected binding.
- We conclude that the SP receptor in rabbit corneal epithelial cells is NK1 and that this receptor participates in the synergistic enhancement of corneal epithelial migration by SP and IGF-1. The precise mechanism(s) of this interaction requires more study. These findings imply that both neural and humoral factors are essential for the maintenance and healing of corneal epithelium.
998.
R A Qasabian C Schyvens R Owe-Young J P Killen P S Macdonald A D Conigrave D J Williamson 《British journal of pharmacology》1997,120(4):553-558
- We have identified the P2 receptors mediating vasomotor responses in the rabbit pulmonary artery.
- Neither ATP nor UTP contracted intact or endothelium-denuded rings. However, both relaxed intact rings of rabbit pulmonary artery that had been preconstricted with phenylephrine (pD2 5.2 and 5.6, respectively).
- The vasodilator effect of UTP was endothelium-dependent and abolished by the nitric oxide synthase inhibitor NG-nitro-L-arginine (L-NOARG).
- The vasodilator effect of ATP was only partially inhibited by removal of endothelium or addition of L-NOARG, suggesting an additional direct effect on vascular smooth muscle.
- The endothelium-dependent vasodilator responses to UTP and ATP were competitively antagonized by suramin.
- Preconstricted, endothelium-denuded rings were also relaxed by 2-methylthio ATP (pD2 6.6), a P2Y receptor agonist.
- Ca2+-mobilizing P2U receptors were identified on smooth muscle cells on the basis of single cell responses to ATP (pD2 7.8) and UTP (pD2 7.9; 6.7 in the presence of 100 μM suramin).
- There was no evidence of a Ca2+-mobilizing P2Y receptor in these cultured cells.
- The data suggest the presence of (i) a suramin-sensitive P2U receptor on endothelial cells that induces vasorelaxation through NO release, (ii) a suramin-sensitive P2U receptor on cultured smooth muscle cells that mobilizes Ca2+ but is not coupled to vasomotor responses and (iii) a putative P2Y receptor on vascular smooth muscle cells that induces relaxation via a Ca2+-independent signal transduction pathway.
999.
M. Wang H. Dotzlaw S.A.W. Fuqua L.C. Murphy 《Breast cancer research and treatment》1997,44(2):145-151
A novel ER-like mRNA containing a 69 nucleotideinsertion precisely between exon 5 and 6 sequenceswas previously identified in human breast cancer biopsysamples. Data are presented which suggest that the69 nucleotide sequence is normally present in intron5 of the human estrogen receptor gene. Theregion corresponding to and surrounding this 69 nucleotidesequence was cloned and the nucleotide sequence determined.Cloning and sequencing of the corresponding region ingenomic DNA isolated from a breast tumor expressingthe 69 nucleotide inserted ER mRNA, revealed anAG point mutation immediately 3 to the69 nucleotide sequence. This point mutation resulted inthe generation of a consensus splice donor site.A consensus splice acceptor site sequence is normallypresent immediately 5 to the 69 nucleotide sequence.These data are consistent with the 69 nucleotidesequence being recognized as an exon by thesplicing machinery, and resulting in processing of amature ER mRNA containing the 69 nucleotide insert. 相似文献
1000.
Carol A. Faaland Sreedevi Adhikarakunnathu Thresia Thomas T.J. Thomas 《Breast cancer research and treatment》1997,44(1):47-56
Tyrphostins are a group of compounds specifically targeted for the inhibition of tyrosine phosphorylation in signal transduction pathways. We studied the effects of a tyrphostin, 3,4-dihydroxy--cyanothiocinnamamide (tyrphostin-47), on hormone-responsive MCF-7 and hormone-unresponsive MCF-7-5C cell growth by DNA analysis for a period of 10 days. The growth of both cell lines was inhibited by this drug at 50 and 100 µM concentrations. Flow cytometric analysis showed that tyrphostin treatment caused a significant delay in the progression of MCF-7 cells through Gl and S phases of the cell cycle. The level of cyclin B1, a component of the mitosis promoting factor (MPF), was reduced by 90% in the presence of 100 µM tyrphostin. The other component of MPF, p34cdc2 kinase, was not affected; however, its functional activity was dramatically reduced, as determined by histone H1 phosphorylation assay. In contrast, G1 cyclins (D1 and E) and tyrosine kinase activity were not markedly affected by tyrphostin-47, as determined by Western immunoblot detection with specific antibodies. Our results suggest that a possible mechanism of tyrphostin action in breast cancer cells might involve the suppression of cyclin B1 and inhibition of the functional activity of cyclin B1/p34cdc2 complex. Our data indicate that the cell cycle machinery might be a target for developing novel drugs for breast cancer. 相似文献