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11.
cAMP对胰岛素刺激的NIH3T3细胞丝裂原激活蛋白激酶活性的抑制作用 总被引:1,自引:0,他引:1
目的 探讨cAMP-PKA信号途径对胰岛素激活的Ras-丝裂原激活蛋白激酶(MAPK)信号途径的影响。方法 以3-异丁基-1-甲基黄嘌呤(IBMX)提高细胞内环腺苷酸(cAMP)浓度,藉四唑蓝比色法(MTT法)和蛋白免疫印迹试验分别观察cAMP对胰岛素刺激的小鼠成纤维细胞(NIH3T3细胞)的生长增殖和胞内丝裂原激活蛋白激酶(MAPK)活性的影响。结果 IBMX(0.5mmol/L)抑制静息的和胰岛素(10mU/mL)刺激的NIH3T3细胞的增殖,作用呈时间依赖性。在胰岛素(10mU/mL)刺激的NIH3T3细胞,MAPK出现酪氨酸磷酸化;而以IBMX(0.5mmol/L)预处理细胞30min后,再以胰岛素作用10min,胰岛素刺激的MAPK的酪氨酸磷酸化受抑制。结论:cAMP可通过抑制MAPK磷酸化活化对NIH3T3细胞增殖起抑制作用。 相似文献
12.
Tomohiko Ai M. Horie Kazuhiko Obayashi Shigetake Sasayama 《Pflügers Archiv : European journal of physiology》1998,436(2):168-174
To examine mechanism(s) underlying the accentuated antagonism by angiotensin II (A-II) on twitch tension, we recorded L-type
Ca2+ currents (I
Ca,L) using conventional patch-clamp techniques in single, guinea-pig, ventricular myocytes. I
Ca,L was recorded by a step-pulse protocol after eliminating K+ conductances (internal Cs+ plus tetraethylammonium chloride and K+-free extracellular solution). A-II (100 nM) did not affect basal I
Ca,L, but inhibited I
Ca,L that had been enhanced (approximately 200% of control) by (ISO, isoproterenol 100 nM). The inhibitory action of A-II was
concentration dependent (concentration eliciting 50% inhibition 88±9 pM, n=41) and the ISO-enhanced component of I
Ca,L was completely blocked by A-II at concentrations above 10 nM. CV-11974 (500 nM), an A-II type-1 receptor (AT1) antagonist, prevented the inhibitory action of A-II. Pre-incubation with pertussis toxin (PTX) abolished the inhibitory
effect of A-II. A-II also inhibited the I
Ca,L enhanced by histamine (500 nM) and forskolin (1 μM), but failed to affect I
Ca,L enhanced by intracellular cyclic adenosine monophosphate (1 mM). The inhibitory action of A-II may therefore involve AT1 receptors/PTX-sensitive, guanine nucleotide-binding (G) proteins (Gi)/adenylate cyclase and partially explains the A-II-dependent
accentuated antagonism of inotropy. 相似文献
13.
Debora Steiner Tomer Avidor-Reiss Ester Schallmach Daniella Saya Zvi Vogel 《Journal of molecular neuroscience : MN》1996,27(2):195-203
It was shown previously that chronic exposure to opiate agonists increases adenylyl cyclase (AC) activity, a phenomenon termed
AC superactivation (or supersensitization). More recently, we showed that acute Gi/o-coupled receptor activation inhibits the activity of several AC isozymes, including Ca2+/calmodulin-stimulated AC-I and -VIII, whereas chronic receptor activation induces their superactivation. Here, we report
that both acute μ-opioid receptor-induced inhibition and chronic induced superactivation of AC-I and -VIII are pertussis toxin
sensitive. In addition, we show that proteins that interfere with the activity of {ie195-2} subunits ({ie195-3} scavengers)
strongly attenuate the acute inhibition of AC-I and -VIII and the superactivation of AC-I, and abolish the superactivation
of AC-VIII. Based on these results, we suggest that {ie195-4} is involved in the acute inhibition and chronic agonist-induced
superactivation of AC types I and VIII. 相似文献
14.
15.
Laura Santambrogio Maria Lipartiti Alessandro Bruni Roberto Dal Toso 《Journal of neuroimmunology》1993,45(1-2)
The presence of functional dopamine receptors on differentiated cells of the mammalian immune system is still under discussion. This study has utilized (-)-[3H]sulpride as a ligand to detect the presence of recognition sites of the dopamine D2 receptor family on human T- and B-lymphocytes. The (-)-[3H]sulpiride binding was of high affinity (Kd 0.9 nM ± 0.2 nM, specific, saturable (Bmax 10.2 ± 1.4 fmol/106 cells) and reversible. The pharmacological characterization of the recognition site suggests, similarities mainly with the D2 and D4 rather than D3 subtype of dopamine receptor. Furthermore, dopamine treatment was able to reduce the intracellular cAMP levels of lymphocytes stimulated with forskolin, thus suggesting a potential functional significance of this dopamine receptor in mediating neural-immune interactions. 相似文献
16.
17.
Noradrenaline- and Enkephalin-Induced Inhibition of Voltage-Sensitive Calcium Currents in NG108-15 Hybrid Cells 总被引:4,自引:0,他引:4
Voltage-sensitive calcium currents were recorded from chemically differentiated neuroblastoma x glioma hybrid (NG108-15) cells using the whole-cell clamp technique. Both noradrenaline and [D-Ala2, D-Leu5] enkephalin (DADLE) reversibly depressed the amplitude of the calcium current by up to 30%. The response to noradrenaline occluded that to DADLE suggesting that both agonists depress the same fraction of current. The response to DADLE but not that to noradrenaline desensitized rapidly. Cells responded normally to noradrenaline when desensitized to the opioid. Responses to either agonist were absent in cells pre-incubated with pertussis toxin. In addition the response to noradrenaline became irreversible in cells dialysed internally with a non-hydrolysable analogue of GTP. The response to noradrenaline was not affected by treatment of the cells with either membrane-permeable analogues of cAMP or a combination of forskolin and isobutylmethylxanthine. It is concluded that both noradrenaline and DADLE depress the same fraction of voltage-dependent calcium current in NG108-15 cells; that the responses are mediated by a pertussis-sensitive GTP-binding protein but are not secondary to a reduction in the intracellular concentration of cAMP; and that desensitization of the opioid response occurs at a site linked intimately to the opioid receptor rather than at a common site in the transduction pathway between receptor activation and reduction in the calcium channel current. 相似文献
18.
The gastrointestinal prokinetic benzamide derivatives are agonists at the non-classical 5-HT receptor (5-HT4) positively coupled to adenylate cyclase in neurons 总被引:24,自引:0,他引:24
Aline Dumuis Michèle Sebben Joël Bockaert 《Naunyn-Schmiedeberg's archives of pharmacology》1989,340(4):403-410
Summary We have previously shown that a non-classical 5-hydroxytryptamine (5-HT4) receptor mediates the stimulation of adenylate cyclase activity in mouse embryo colliculi neurons in primary culture. The pharmacological characteristics of this receptor exclude the possibility that it belongs to the known 5-HT1, 5-HT2 or 5-HT3 receptor types. Here we report that this 5-HT receptor can be stimulated by 4-amino-5-chloro-2-methoxy substituted benzamide derivatives. All these compounds have been reported to be potent stimulants of gastrointestinal motility and some of them are 5-HT3 receptor antagonists. The rank order of potency of these substituted benzamide derivatives in stimulating cAMP formation was: cisapride > BRL 24924 > 5-HT > zacopride > BRL 20627 > metoclopramide. The non-additivity of benzamide and 5-HT activities suggests that 5-HT and the substituted benzamide derivatives act on the same receptor. Only ICS 205930, a recognized 5-HT3 receptor antagonist, competitively antagonized the stimulatory effect of cisapride, zacopride and BRL 24924. However, its pK
i (6–6.3) for this new receptor was very different from its pK
i for 5-HT3 receptors (pK
i = 8 –10). Other selective 5-HT3 receptor antagonists with an indole group (BRL 43694 and GR 38032F), with a benzoate group (cocaïne, MDL 72222) or with a piperazine group (quipazine) were ineffective in reversing the stimulatory effect of benzamide derivatives. Exposure of neuronal cells to potent agonists at this receptor such as BRL 24924 rapidly reduces its capacity to stimulate cAMP production. For example, a preincubation of 10 min with BRL 24924 (100 mol/l) reduced by 42% the ability of 5-HT to stimulate cAMP production. Cross-desensitization occurs between the effects of 5-HT and benzamides. The unique pharmacology of these nonclassical 5-HT receptors that we propose to call 5-HT4 is very close and even identical to the pharmacology of the high affinity 5-HT receptors involved in the indirect stimulation of smooth muscle in the guinea pig ileum. These receptors are different from the 5-HT3 receptors also present in guinea pig ileum.Send offprint requests to A. Dumuis at the above address 相似文献
19.
Angiotensin-(1–7) stimulates water transport in rat inner medullary collecting duct: evidence for involvement of vasopressin V2 receptors 总被引:1,自引:0,他引:1
Magaldi AJ Cesar KR de Araújo M Simões e Silva AC Santos RA 《Pflügers Archiv : European journal of physiology》2003,447(2):223-230
The peptide angiotensin-(1–7) [Ang-(1–7)] is known to enhance water transport in rat inner medullary collecting duct (IMCD). The aim of this study was to determine the mechanism of the Ang-(1–7) effect on osmotic water permeability (P
f). P
f was measured in the normal rat IMCD perfused in vitro in presence of agonists [Ang-(1–7), arginine vasopressin (AVP) and Ang-(3–8)], and antagonists of the angiotensin and the vasopressin cascade. Ang-(1–7), but not Ang-(3–8), increased P
f significantly. The effect of Ang-(1–7) on P
f was abolished by its selective antagonist, A-779, added before or after Ang-(1–7). Prostaglandin E2 and the protein kinase A inhibitor H8 also blocked the Ang-(1–7) effect. Blockade of vasopressin V1 receptors by antagonists did not change the Ang-(1–7) effect, but pre-treatment with a V2 antagonist abolished the effect of Ang-(1–7) on P
f. Similarly, pre-treatment with A-779 inhibited AVPs effect on P
f. Forskolin-stimulated P
f was blocked both by A-779 and by the V2 antagonist. Finally, Ang-(1–7) increased cAMP levels in fresh IMCD cell suspensions whilst the forskolin-stimulated cAMP synthesis was decreased by A-779 and the V2 antagonist. These data provide evidence that Ang-(1–7) interacts via its receptor with the AVP V2 system through a mechanism involving adenylate-cyclase activation. 相似文献
20.
Effects of prostaglandin E2 on Th0-type human T cell clones: modulation of functions of nuclear proteins involved in cytokine production 总被引:3,自引:0,他引:3
Watanabe Sumiko; Yssel Hans; Harada Yoshio; Arai Ken-ichi 《International immunology》1994,6(4):523-532
The effects of prostaglandin E2 (PGE2) on cytokine productionand proliferation of the CD4+ human helper T cell clone SP-B21were investigated. In cells stimulated with antl-CD3 mAb, PGE2inhibited cell proliferation and the production of all the cytokinesexamined. Addition of rlL-2 fully restored the prollferatlveresponse and partially restored the production of IL-4 and IL-5,but not that of other cytokines. In contrast, In cells stimulatedwith phorbol myrlstate acetate (PMA)/A23187, PGE2 enhanced theproduction of IL-4 and IL-5, and only partially inhibited theproduction of other cytokines. Therefore, the effects of PGE2vary depending on the mode of T cell activation, and the IL-4and IL-5 are regulated differently from other cytokines. Ina mobility shift assay, only the NF-B (p50/p5O) homodlmer wasobserved in a complex formed with the B sequence in unstlmulatedSP-B21 cells. When cells were stimulated with antl-CD3 mAb orPMA/A23187, a complex formation of NF-B (p50/p65) heterodlmerwith the B sequence was induced. Interestingly, PGE2 or di-butyryl(Bt2cAMP abolished the binding of NF-B (p50/p65) heterodlmerto the B sequence in cells stimulated with antl-CD3 mAb butnot with PMA/A23187. Our results suggest that the target ofPGE2 action is a component in the signal transductlon pathwayleading to the activation of protein klnase C. However, theinhibition of the T cell activation signals by PGE2 is selective.PGE2 enhanced the complex formation with NF-AT, AP-1 and CLEOsequences when the cells were activated by either anti-CD3 mAbor PMA/A23187 stimulation. It seems therefore that PGE2, byelevating cAMP levels, interferes with the activation pathwayfor NF-B but not for NF-AT, AP-1 or CLEO binding protein. 相似文献