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101.
Pafenolol is a -blocker with unusual oral absorption properties. The blood concentration–time profile exhibits two peaks, and the bioavailability is low and dose dependent because of incomplete and nonlinear intestinal uptake. We addressed the question whether the intestinal absorption of pafenolol was affected by bile depletion in the gut lumen of rats. Further, the hypothesis that variable gastric emptying accounts for double peaks in blood was tested by duodenal administration of pafenolol. Following intraduodenal administration to rats with intact bile secretion, double peaks were observed in the blood concentration–time curve. The bioavailability was 6.8 ± 0.7% for the low dose (1 µmol/kg) and increased significantly to 28 ± 10% following the high duodenal dose (25 µmol/kg). These blood concentration–time profiles exclude interrupted gastric emptying as cause of the twin peaks. In bile duct-cannulated rats the intestinal absorption of the low dose (1 µmol/kg) was still poor (F = 10.7 ± 5.5%) and the blood concentration–time profile contained two peaks. Following administration of a high duodenal dose (25 µmol/kg) to rats with an almost bile-free small intestine, the absorption rate increased and the double-peak phenomenon disappeared in five of seven rats, while the bioavailability increased significantly, to 62 ± 27%. These results suggest that the low bioavailability of pafenolol is due to a complexation between bile and pafenolol in the gut lumen, preventing intestinal uptake in the major part of the small intestine. Further, such complex formation in the intestinal lumen may be the underlying mechanism of the double peaks observed in the blood concentration–time profile. 相似文献
102.
异丙酚与氯胺酮联合应用的实验研究 总被引:4,自引:0,他引:4
目的;研究异丙酚(propofol,P)和氯胺酮(ketamine,K)的相互作用。方法:观察P对K引起的小鼠入睡率及睡眠时间的影响;研究P对K镇痛效应的影响;以序贯法研究不同剂量的P对小鼠静脉注射K的半数致死量(LD50)的影响,并探讨P对清醒家兔静注K的呼吸循环效应的影响。结果:P可增大K引起的小鼠入睡率(P<0.01);延长小鼠睡眠时间(P<0.01),且呈剂量依赖关系;种测痛方法均显示P增强K的镇痛作用(P<0.05);P可拮抗兔静注K所致的血压高和心率增快效应(P<0.01),而加重K的呼吸抑制作用(P<0.01)。在所用剂量范围内P对小鼠静注K的LD50无明显影响。结论:P可增强K的催眠和镇痛作用,拮抗K的循环兴奋作用,而不减小K的LD50。提示二者合用于临床静脉复合全麻是合理的,但需注意呼吸的管理。 相似文献
103.
104.
Compared to the charge–charge interaction, the role of the dipole-dipole interaction has long been ignored in the phase behaviors of charged macromolecules in solutions. Charged macromolecules in solutions exhibit rich phase behaviors due to their complexity and they have been studied extensively. Phase separation can happen for charged macromolecules in the presence of monovalent salt, multivalent salt, and oppositely charged polymers, surfactants, etc., and for more advanced charged macromolecules such as polyzwitterions and polyampholytes, the phase diagram is even richer. In this perspective, the unacknowledged role of dipole-dipole interaction in the phase behaviors of charged macromolecular solutions will be introduced. Dipolar polymers can form complex, self-regulating structures which can be employed in various fields from drug-delivery systems to next-generation polymers. More importantly, it will shed light on how some of the life's basic and coherent structures such as biomolecular condensates and membrane-less organelles are assembled and built by charged biomacromolecules such as DNA, RNA, and proteins. 相似文献
105.
R. Jackisch H. Hotz C. Allgaier G. Hertting 《Naunyn-Schmiedeberg's archives of pharmacology》1994,349(3):250-258
Slices of the rabbit caudate nucleus, preincubated with [3H]dopamine and subjected to electrical field stimulation, were used (1) to investigate the involvement of G-proteins in the signal transduction of presynaptic D2 (auto)receptors and -opioid receptors on dopaminergic axon terminals in this tissue and (2) to study a possible mutual interaction of these two presynaptic receptors. Pretreatment of the slices with either pertussis toxin (8 g/ml; 18 h), or N-ethylmaleimide (30 M, 30 min) significantly reduced the inhibitory effects of both the D2 agonist quinpirole and the -opioid receptor agonist U-50488H on the [3H]overflow evoked by 36 pulses (2 ms, 24 mA, 0.3 Hz), suggesting the coupling of both receptors to G-proteins.Experiments designed to study possible interactions of these two presynaptic receptors were carried out under stimulation conditions (only 1 pulse), which strongly diminish interference of endogenous transmitters released in the tissue with modulatory effects of exogenous drugs. For instance, due to the presence of endogenous dopamine, quinpirole was much less potent during 36-pulse-than during 1-pulse field stimulation, whereas the D2 antagonist domperidone was almost without effect in the latter case. Using the 1-pulse stimulation paradigm, the concentration/response curve of quinpirole was unaffected in the presence of the halfmaximal inhibitory concentration of U-50,488 H (0.1 M). On the other hand, also quinpirole at its halfmaximal inhibitory concentration (0.1 M), hardly affected the concentration/response curve of U-50,488 H: only high concentrations of U-50,488 H (above 1 M) seemed to be slightly less effective in the presence than in the absence of the D2 agonist. U-50,488 H, at these high concentrations, was also less potent under 36-pulse than under 1-pulse stimulation conditions. From these findings, we conclude that there is only a limited interaction between presynaptic D2 autoreceptors and -opioid receptors on dopaminergic axon terminals in the rabbit caudate nucleus, despite they are both coupled to PTX/NEM-sensitive G-proteins.
Correspondence to: R. Jackisch at the above address 相似文献
106.
The selectivity of different external binding sites for quaternary ammonium ions in cloned potassium channels 总被引:1,自引:0,他引:1
W. Jarolimek K. V. Soman M. Alam A. M. Brown 《Pflügers Archiv : European journal of physiology》1995,430(5):672-681
Tetraethylammonium (TEA) is thought to be the most effective quaternary ammonium (QA) ion blocker at the external site of K+ channels, and small changes to the TEA ion reduce its potency. To examine the properties of the external QA receptor, we applied a variety of QA ions to excised patches from human embryonic kidney cells or Xenopus oocytes transfected with the delayed rectifying K+ channels Kv 2.1 and Kv 3.1. In outside-out patches of Kv 3.1, the relative potencies were TEA > tetrapropylammonium (TPA) > tetrabutylammonium (TBA). In contrast to Kv 3.1, the relative potencies in Kv 2.1 were TBA > TEA > TPA. In Kv 3.1 and Kv 2.1, external tetrapentylammonium (TPeA) blocked K+ currents in a fast, reversible and, in contrast to TEA, time-dependent manner. The external binding of TPeA appeared to be voltage independent, unlike the effects of TPeA applied to inside-out patches. External n-alkyl-triethylammonium compounds (C8, C10 chain length) had a lower affinity than TEA in Kv 3.1, but a higher affinity than TEA in Kv 2.1. In Kv 3.1, the decrease in QA affinity was large when one or two methyl groups were substituted for ethyl groups in TEA, but minor when propyl groups replaced ethyl groups. Changes in the free energy of binding could be correlated to changes in the free energy of hydration of TEA derivatives calculated by continuum methodology. These results reveal a substantial hydrophobic component of external QA ion binding to Kv 2.1, and to a lesser degree to Kv 3.1, in addition to the generally accepted electrostatic interactions. The chain length of hydrophobic TEA derivatives affects the affinity for the hydrophobic binding site, whereas the hydropathy of QA ions determines the electrostatic interaction energy. 相似文献
107.
R. K. Verbeeck J. I. Macdonald S. M. Wallace R. J. Herman 《European journal of clinical pharmacology》1995,47(6):519-523
The effect of probenecid on the pharmacokinetics of diflunisal and its glucuronide and sulphate conjugates was studied in 8 healthy volunteers. Diflunisal 250 mg b. d. was administered p. o. for 15 days and its steady state pharmacokinetics was evaluated on Day 16 after the last dose (control phase). Probenecid 500 mg b. d. was co-administered throughout the entire study period in the treatment phase of the study.The steady state plasma concentration of diflunisal was significantly higher during the probenecid treatment phase as compared to the control phase (104.0 vs. 63.1 g·ml–1). This was the result of a significant decrease in the plasma clearance of diflunisal from 5.8 (control) to 3.4 ml·min–1 (probenecid co-administration). The metabolite formation clearances of both glucuronides were significantly decreased by probenecid, -45 % and -54 % for the phenolic and acyl glucuronide, respectively. The metabolite formation clearance of the sulphate conjugate was not affected by probenecid co-administration.Steady state plasma concentrations of the sulphate and glucuronide conjugates of diflunisal were 2.5- to 3.1-fold higher during probenecid co-administration, due to a significant reduction in the renal clearance of the three diflunisal conjugates. Probenecid also reduced the plasma protein binding of diflunisal, but only to a minor extent; the unbound plasma fraction of diflunisal at steady state averaged between 5 and 30 % higher during probenecid co-administration. 相似文献
108.
Bakhtin's Philosophy and Medical Practice — Toward a Semiotic Theory of Doctor — patient Interaction
Puustinen R 《Medicine, health care, and philosophy》1999,2(3):275-281
Doctor-patient interaction has gained increasing attention among sociologists and linguists during the last few decades. The
problem with the studies performed so far, however, has been a lack of a theoretical framework which could bring together
the various phenomena observed within medical consultations. Mikhail Bakhtin's philosophy of language offers us tools for
studying medical practice as socio-cultural semiotic phenomenon. Applying Bakhtin's ideas of polyphonic, context-dependent
and open-ended nature of human communication opens the possibilities to develop prevailing theoretical and empirical approaches
to the study of medical consultations.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
109.
Verdonck P Vierendeels J Riemslagh K Dick E 《Medical & biological engineering & computing》1999,37(4):511-516
Both invasive left-ventricular pressure measurements and non-invasive colour M-mode echographic measurements have shown the existence of intraventricular pressure gradients (IVPGs) during early filling. The mechanisms responsible for these IVPG cannot be completely explained by the experiments. Therefore a one-dimensional numerical model is developed and validated. The model describes filling (both velocities and pressures) along a left ventricular (LV) base-apex axis. Blood-wall interaction in the left ventricle with moving boundaries is taken into account. The computational results for a canine heart indicate that the observed IVPGs during filling are the consequence of a complex interaction between, on the one hand, pressure waves travelling in the LV and, on the other hand, LV geometry, relaxation and compliance. The computational results indicate the pressure dependency of wavespeed (0.77-1.90 m-1 s) for different mean intraventricular pressures (0.88-5.00 mmHg) and IVPGs up to 2 mmHg, independent of the ratio of end systolic volume and equilibrium volume. Increasing relaxation rate not only decreases minimum basal pressure (2.8 instead of 3.6 mmHg) but also has a strong influence on the time delay between the minimum basal and apical pressures (14 ms instead of 49 ms). The results sustain the hypothesis that pressure-wave propagation determines IVPGs and that IVPGs are no proof of elastic recoil. 相似文献
110.
Extracellular 4-aminopyridine (4-AP), tetraethylammonium chloride (TEA) and quinine depolarized the neuropile glial cell membrane and decreased its input resistance. As 4-AP induced the most pronounced effects, we focused on the action of 4-AP and clarified the ionic mechanisms involved. 4-AP did not only block glial K+ channels, but also induced Na+ and Ca2+ influx via other than voltage-gated channels. The reversal potential of the 4-AP-induced current was -5 mV. Application of 5 mM Ni2+ or 0.1 mM d-tubocurarine reduced the 4-AP-induced depolarization and the associated decrease in input resistance. We therefore suggest that 4-AP mediates neuronal acetylcholine release, apparently by a presynaptic mechanism. Activation of glial nicotinic acetylcholine receptors contributes to the depolarization, the decrease in input resistance, and the 4-AP-induced inward current. Furthermore, the 4-AP-induced depolarization activates additional voltage-sensitive K+ and Cl- channels and 4-AP-induced Ca2+ influx could activate Ca2+-sensitive K+ and Cl- channels. Together these effects compensate and even exceed the 4-AP-mediated reduction in K+ conductance. Therefore, the 4-AP-induced depolarization was paralleled by a decreasing input resistance. 相似文献