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21.
Kenichiro Mikawa Hiroaki Kume Kenzo Takagi 《Clinical and experimental pharmacology & physiology》1997,24(2):175-181
1. In order to examine the mechanisms of cGMP-induced relaxation in airway smooth muscle, the effects of atrial natriuretic peptide (ANP) and 8-brom cGMP on muscle tone were studied by measuring isometric tension, while the effects on cytosolic Ca2+ concentrations were studied by measuring the spectra of fura-2 loaded in guinea-pig tracheal strips. 2. Atrial natriuretic peptide and 8-brom cGMP caused a concentration-dependent inhibition of spontaneous tone in the guinea-pig trachea. The relaxant effects of these agents on spontaneous tone were markedly suppressed in the presence of iberiotoxin (IbTX), a selective inhibitor of large-conductance Ca2+-activated K+ (BKca) channels. Iberiotoxin (30 nmol/L) markedly affected the maximal effect induced by ANP and 8-brom cGMP and augmented EC70 values for ANP and EC50values for 8-brom cGMP approximately 27- and 17-fold, respectively. The inhibitory effects of IbTX on relaxation induced by these agents were diminished in the presence of 1 μmol/L nifedipine, an antagonist of voltage-operated Ca2+channels (VOCC). 3. The inhibitory action of ANP and 8-brom cGMP on spontaneous tone was not affected by the presence of 10 μmol/L glibenclamide, an inhibitor of ATP-sensitive K+ channels, and 100 nmol/L apamin, an inhibitor of small-conductance Ca2+-activated K+ channels. When these agents were applied to tissues precontracted by high (40mmol/L) K+, the relaxant effects of these agents markedly diminished. 4. The extracellular Ca2+-dependent contraction was inhibited in the presence of 0.3 μmoI/L ANP or 0.1 mmol/L 8-brom cGMP. Concentration—response curves to extracellular Ca2+ (0.03—2.4 mmol/L) were markedly diminished by exposure to these agents. The maximal effect induced by extracellular Ca2+ was affected by these agents. 5. Atrial natriuretic peptide caused an inhibition of spontaneous tone accompanied by a reduction in the intracellular Ca2+ concentration. In the presence of IbTX, the elimination of both muscle tone and cytosolic Ca2+ by ANP was suppressed. 6. We conclude that ANP and 8-brom cGMP activate BKca channels and that the inhibition of Ca2+ influx through VOCC, mediated by BKca channel activation, may be involved in cGMP-dependent bronchodilation. 相似文献
22.
Using the whole-cell configuration of the patch clamp technique, calcium-activated potassium currents (IK,Ca) were investigated in ramified murine brain macrophages. In order to induce IK,Ca the intracellular concentration of nominal free Ca2+ was adjusted to 1μM. The Ca2+-activated K+ current of brain macrophages did not show any voltage dependence at test potentials between –120 and +30mV. A tenfold change
in extracellular K+ concentration shifted the reversal potential of IK,Ca by 51mV. The bee venom toxin apamin applied at concentrations of up to 1μM did not affect IK,Ca. Ca2+-activated K+ currents of ramified brain macrophages were highly sensitive to extracellularly applied charybdotoxin (CTX). The half-maximal
effective concentration of CTX was calculated to be 4.3nM. In contrast to CTX, the scorpion toxin kaliotoxin did not inhibit
IK,Ca at concentrations between 1 and 50nM. Tetraethylammonium (TEA) blocked 8.0% of IK,Ca at a concentration of 1mM, whereas 31.4% of current was blocked by 10mM TEA. Several inorganic polyvalent cations were tested
at a concentration of 2mM for their ability to block IK,Ca. La3+ reduced IK,Ca by 72.8%, whereas Cd2+ decreased IK,Ca by 17.4%; in contrast, Ni2+ did not have any effect on IK,Ca. Ba2+ applied at a concentration of 1mM reduced IK,Ca voltage-dependently at hyperpolarizing potentials.
Received: 17 January / Accepted: 5 May 1997 相似文献
23.
Sources of P300 attenuation after head injury: Single-trial amplitude, latency jitter, and EEG power
Single trial amplitude, latency jitter, and electroencephalographic (EEG) power were examined as sources of the group difference in averaged P300 amplitude among 15 traumatically brain injured and 20 control individuals in an auditory oddball paradigm. Mean amplitude of the individual trials was highly correlated with the amplitude of the averaged P300, with little additional unique variance attributable to latency jitter or EEG power. The group difference in P300 amplitude was also explained by the mean amplitude of the single trials. These results support the robustness of the event-related potential averaging technique within the paradigm used. 相似文献
24.
25.
Abstract: We analyzed the expression of CEA, CA19-9, CA125, CA15-3 (DF3), PCNA and p53 immunohistochemically in 14 tissue specimens of mucosal cancers in adenoma, seven tubulovillous adenoma specimens, and 16 tubular adenoma specimens. The rates of positive staining for mucosal cancer in adenoma, tubulovillous adenoma and tubular adenoma specimens, respectively, were: for CEA: 100%, 85.7% and 75%; for CA19-9: 71.4%, 71.4% and 56.2%; for CA125:0%, 0% and 0%;for CA15-3 (DF3): 64.3 %, 0% and 0 %; for PCNA: 100%, 88.9% and 56.2%; and for p53: 35.7%, 0% and 0% . The results suggest that the expressions of CEA, CA19-9, CA15-3 (DF3), PCNA and p53 are related to colorectal tumorigenesis. None of the specimens studied showed staining for CA125, suggesting that CA125 is not involved in the early stages of colorectal carcinogenesis. There was no significant difference in the rates of positive staining for CEA and CA19-9 among mucosal cancer in adenoma, tubular adenoma and tubulovillous adenoma specimens. However, the rates of positive staining for PCNA and p53 were significantly higher in mucosal cancer in adenoma specimens than for tubular adenoma specimens (p<0.05), and the rate of CA15-3 (DF3) positive staining was significantly higher for mucosal cancer in adenoma than for tubulovillous adenoma (p<0.01) and tubular adenoma (p< 0.001) specimens. Therefore, the CA15-3 (DF3) antigen is an immunohistochemical marker for colorectal carcinomas. The present results suggest that CA15-3 (DF3), PCNA and p53 play important roles in the genesis of colorectal adenomas. 相似文献
26.
Rolf W. Hartmann Martin Frotscher Dorothea Ledergerber Gerald A. Wchter Gertrud L. Grün Tom F. Sergejew 《Archiv der Pharmazie》1996,329(5):251-261
In search of potential drugs for the treatment of estrogen- and androgen-dependent cancer as well as the prophylaxis of metastases, tetralones, tetralins, and dihydronaphthalenes bearing a OCH3 substituent at the benzene nucleus and an imidazol-4-yl, imidazol-1-yl, or 1,2,4-triazol-1-yl substituent in 2-position were synthesized with and without C1-spacer between the rings (compounds 2 – 26 ). The compounds were tested in vitro for inhibition of the three target enzymes P450 arom (human placental microsomes), P450 17 (rat testicular microsomes), and P450 TxA2 (citrated human whole blood). To examine selectivity, some compounds were further tested in vitro for inhibition of P450 18 (bovine adrenal mitochondria), P450 see (bovine adrenal mitochondria) and corticoid formation (aldosterone, corticosterone; ACTH stimulated rat adrenal tissue). In vivo, selected compounds were examined in Sprague Dawley rats regarding P450 TxA2 inhibition, reduction of plasma testosterone concentration, antiuterotrophic activity (inhibition of the uterotrophic activity of androstenedione), reduction of plasma estradiol concentration (pregnant mares' serum gonadotropin-primed rats), and mammary tumor inhibiting activity (dimethylbenzanthracene-induced tumor; pre- and postmenopausal model). In the series of imidazol-4-yl compounds, which represent a novelty in the field of azole inhibitors of steroidogenic P450 enzymes, strong inhibitors of P450 arom and/or P450 17 were found: 7-OCH3-2-(imidazol-4-ylmethylene)-1-tetralone ( 4 ) and 7-OCH3-2-(imidazol-4-ylmethyl)-tetralin ( 12 ) are among the most potent inhibitors of P450 arom in vitro known so far. Compound 4 is a selective inhibitor, whereas 12 shows in addition strong inhibition of P450 17. In contrast to 12 , the 6-OCH3 derivative (compound 11 ) is a selective inhibitor of P450 17, being 50 times more potent than ketoconazole. Some imidazol-1-yl compounds show a marked inhibition of P450 TxA2: 2-(imidazol-1-ylmethyl)-1-tetralone ( 13 ) is a selective inhibitor of P450 TxA2, whereas 7-OCH3-2-(imidazol-1-ylmethyl)-tetralin ( 17 ) as well as 2-(imidazol-1-ylmethyl)-tetralin ( 16 ) and 7-OCH3-2-imidazol-1-yl-3,4-dihydronaphthalene ( 25 ) additionally show strong inhibition of P450 arom and P450 17. Regarding the other steroidogenic P450 enzymes as well as corticosterone formation, the compounds show only little inhibitory activity. Aldosterone formation, however, is inhibited at low concentrations. Nevertheless, 4 and 12 are more selective, i.e. inhibit aldosterone synthesis less than the well known inhibitor of P450 arom fadrozole. The compounds show activity in the aforementioned in vivo tests. 相似文献
27.
A rapid and sensitive method for measuring monooxygenase activities in hepatocytes cultured in 96-well plates 总被引:3,自引:0,他引:3
Summary Measurement of biotransformation activities in cells is of great importance for drug metabolism and toxicologic studies. It is currently done by measuring the enzymatic activities in partially purified microsomes. In the present work we report on a rapid, easy, sensitive, and reproducible fluorimetric assay for quantifying cytochrome P450-dependent monooxygenase activities (P450IA1, P450IIB1) in hepatocytes cultured in 96-well plates. The procedure involves the direct determination of enzymatic activities in intact hepatocytes while avoiding cell homogenization, thereby permitting use of a the reduced number of cells and allowing cultured cells to be used in later experiments. Substrates (7-ethoxyresorufin, 7-pentoxyresorufin) are added to culture medium and metabolized by hepatocytes. After enzymatic deconjugation, the fluorescent resorufin present in culture medium is quantified by means of a microplate fluorimetric reader. Major advantages of this technique, as compared to other available methods, are: a) no cell disruption is required; b) activity can be measured with a very small number of cells; c) rapid processing time; and d) possibility of performing repeated assays with the same cell monolayer. 相似文献
28.
彩色多普勒在心脏起搏器综合征诊断中的应用价值 总被引:1,自引:1,他引:0
目的 :探讨运用彩色多普勒血流显像 (CDFI)并结合心电图 (ECG)诊断起搏器综合征 (PMS)的临床价值。方法 :对具有详实临床及ECG资料的心室按需 (VVI)起搏器安置患者 6 0例及对照组 4 8例进行CDEI检查 ,观察起搏组与对照组的三尖瓣返流 (TR)的发生率、返流程度 ,并分析二者之间的相关性。结果 :起搏组出现逆传P波 (即PMS阳性 )者 15例 ,CDFI检测出现TR者 2 0例 ,明显高于对照组 ,且PMS阳性者TR发生率明显高于PMS阴性者 ,表明安置VVI起搏器后出现逆传P波与TR的发生相关性良好。结论 :CDFI对PMS的诊断具有重要意义 ,尤其将ECG与CDFI结合应用有助于诊断率的提高。 相似文献
29.
30.
Evidence for the presence of substance P-like immunoreactivity in the human cerebellum 总被引:1,自引:0,他引:1
M. Del Fiacco M. T. Perra M. Quartu M. D. Rosa G. Zucca M. C. Levanti 《Brain research》1988,446(1):173-177
Preliminary results on the localization of substance P-like immunoreactivity in the human cerebellum are presented. Cerebella from newborn and adult subjects were examined. While only sporadic positive fibres were detected in the adult tissue, the immunoreactive material appeared more abundant in the cerebella from newborn subjects. Varicose and non-varicose fibres and dot-like nerve terminals were present with different density in various regions. The paucity of immunoreactive perikarya suggests that most of the cerebellar substance P-like immunoreactive material has an extrinsic origin. 相似文献