全文获取类型
收费全文 | 6978篇 |
免费 | 380篇 |
国内免费 | 195篇 |
专业分类
耳鼻咽喉 | 25篇 |
儿科学 | 51篇 |
妇产科学 | 37篇 |
基础医学 | 709篇 |
口腔科学 | 74篇 |
临床医学 | 314篇 |
内科学 | 528篇 |
皮肤病学 | 90篇 |
神经病学 | 1251篇 |
特种医学 | 391篇 |
外科学 | 285篇 |
综合类 | 457篇 |
预防医学 | 356篇 |
眼科学 | 20篇 |
药学 | 2485篇 |
中国医学 | 199篇 |
肿瘤学 | 281篇 |
出版年
2023年 | 40篇 |
2022年 | 69篇 |
2021年 | 93篇 |
2020年 | 91篇 |
2019年 | 121篇 |
2018年 | 131篇 |
2017年 | 114篇 |
2016年 | 153篇 |
2015年 | 164篇 |
2014年 | 278篇 |
2013年 | 314篇 |
2012年 | 292篇 |
2011年 | 382篇 |
2010年 | 307篇 |
2009年 | 311篇 |
2008年 | 396篇 |
2007年 | 411篇 |
2006年 | 390篇 |
2005年 | 293篇 |
2004年 | 307篇 |
2003年 | 305篇 |
2002年 | 216篇 |
2001年 | 147篇 |
2000年 | 299篇 |
1999年 | 93篇 |
1998年 | 108篇 |
1997年 | 128篇 |
1996年 | 100篇 |
1995年 | 101篇 |
1994年 | 115篇 |
1993年 | 94篇 |
1992年 | 93篇 |
1991年 | 88篇 |
1990年 | 93篇 |
1989年 | 77篇 |
1988年 | 64篇 |
1987年 | 74篇 |
1986年 | 81篇 |
1985年 | 107篇 |
1984年 | 115篇 |
1983年 | 89篇 |
1982年 | 56篇 |
1981年 | 46篇 |
1980年 | 59篇 |
1979年 | 35篇 |
1978年 | 25篇 |
1977年 | 18篇 |
1976年 | 14篇 |
1975年 | 15篇 |
1973年 | 17篇 |
排序方式: 共有7553条查询结果,搜索用时 15 毫秒
71.
The delayed neurotoxic organophosphate, diisopropylfluorophosphate (DFP) binds with high affinity to membrane-bound proteins
from chicken nerve tissues. The autoradiographic distribution of [3H]DFP binding sites in spinal cord sections of chicken showed higher concentrations of binding sites in gray matter than in
white matter. In the cervical region, fairly high densities of [3H]DFP binding sites were found in laminae X and to a lesser extent, in the ventral horn gray matter. To identify the membrane-associated
DFP-binding proteins, detergent-solubilized membranes were labeled widi 5-10nM [3H]DFP (10pmol/mg protein) for 70 min at 37°C. Gel-exclusion chromatography of the [3H]DFP-radiolabeled membranes indicated at least two major radioactive proteins with apparent molecular weights of 150-670
kDa and 40-129 kDa. Although we could not identify the high affinity DFP binding proteins, the autoradiographic experiments
clearly demonstrated that the DFP binding proteins localized on gray matter of chicken spinal cord. 相似文献
72.
Hansen O 《Pflügers Archiv : European journal of physiology》1999,437(4):517-522
Purified Na+/K+-ATPase (EC 3.6.1.37) isolated from the rectal gland of Squalus acanthias was characterized in ouabain-binding studies and with respect to isoform(s) of the α peptide. To avoid enzyme inactivation
[3H]ouabain equilibrium binding was carried out at 20°C. The heterogeneity of Na+/K+-ATPase isolated from shark rectal gland was similar in [3H]ouabain binding as previously seen in hydrolytic studies. The binding isotherms were compatible with the existence of a
high-affinity (K
dis 0.69 nM) and a low-affinity (K
dis 42 nM) component of 1.46 and 0.79 nmol.(mg protein)–1, respectively. In Western blots the α peptide of the enzyme hybridized with an isoform-specific polyclonal antibody raised
to an α3-specific region of the large intracellular domain of rat Na+/K+-ATPase, but not with the supposed α3-specific monoclonal antibody MA3-915 with its epitope near the N-terminus. Semi-quantitative analysis of the reaction of
the α3-specific polyclonal antibody with the α peptide from the shark enzyme compared to the reaction with α peptide from rat brain
enzyme indicated that this region is not exactly the same in the two species. The α peptide of shark enzyme was not recognized
by α1- or α2-specific polyclonal antibodies, or by the α1-specific monoclonal antibodies 3B and F6. The large intracellular domain of Na+/K+-ATPase from shark rectal gland thus seems to be α3-like and no α isoform heterogeneity seems able to account for the heterogeneity seen in ouabain binding.
Received: 7 August 1998 / Accepted: 6 November 1998 相似文献
73.
目的比较肘肌、三角肌、小指展肌重复神经电刺激(RNS)对重症肌无力(MG)的诊断价值。方法应用低频RNS技术对18例MG患者的肘肌、三角肌、小指展肌进行疲劳前后的检测,用DANTECounterpoint肌电图仪记录。结果对照组肘肌、三角肌、小指展肌疲劳前RNS电压分别降低了1.54%±1.32%、1.64%±1.43%、0.62%±0.38%;疲劳后RNS电压分别降低了2.01%±1.75%、2.05%±1.98%、1.02%±0.75%。MG组肘肌、三角肌、小指展肌疲劳前测试阳性分别为9/18(50%)、10/18(55.6%)、3/18(16.7%)(P均<0.05);疲劳后RNS测试阳性分别为15/18(83.3%)、14/18(77.8%)、6/18(33.3%)(P均<0.05)。经卡方检验,肘肌疲劳前后RNS测试阳性率有显著性差异(P<0.05)。小指展肌、三角肌疲劳前后RNS测试阳性率对比无显著性差异。结论MG患者肘肌疲劳后RNS阳性率较疲劳前明显增高,而三角肌、小指展肌疲劳前后RNS阳性率无显著性差异;肘肌、三角肌RNS测试较小指展肌更敏感,但肘肌RNS方法简便,病人不适程度轻,有较大的临床实用价值。 相似文献
74.
75.
R. K. Bentsen-Farmen I. V. Botnen H. Notø J. Jacob S. Øvrebø 《International archives of occupational and environmental health》1999,72(3):161-168
Objective: The objective in our study was to quantitate benzo[a]pyrene (B[a]P) metabolites by a combination of immunoaffinity chromatography and high-pressure liquid chromatography (HPLC) with fluorescence detection in urine from workers exposed to high levels of polycyclic aromatic hydrocarbons (PAH). Furthermore, by the simultaneous quantitation of 1-hydroxypyrene, the correlation between the B[a]P-tetrol and 1-hydroxypyrene would provide a means of evaluating the validity of 1-hydroxypyrene as a surrogate biomarker for occupational exposure to the potent carcinogen B[a]P in an electrode paste plant. Methods: The study was carried out at an electrode paste plant that produces electrode paste for Söderberg electrodes. A total of 34 pre- and post-shift urine samples and 17 personal air samples were collected from 17 workers during a normal work week. The concentration of 1-hydroxypyrene was measured in all urine samples. A recent method of quantitating B[a]P-r-7, t-8, t-9, c-10-tetrol in urine of humans exposed to low levels of PAH has been described. A modified version of this method involving purification of urine samples on immunoaffinity columns and HPLC analysis with fluorescence detection was used on urine samples from workers exposed to high levels of PAH. A monoclonal antibody (8E11) with binding affinity to B[a]P-tetrols was used. This antibody also binds several PAH-DNA adducts and metabolites, including 1-hydroxypyrene. Gas chromatography/mass spectroscopy (GC/MS) was also used for identification of metabolites isolated by HPLC fractionation. Results: From personal air sampling the mean exposure to particulate PAHs was 38?μg/m3. The mean concentration of urinary 1-hydroxypyrene was 3.9?μmol/mol creatinine in preshift samples and 10.2?μmol/mol creatinine in postshift samples. We could not identify detectable amounts of urinary B[a]P-tetrol by HPLC or fluorescence spectroscopy after purification on immunoaffinity columns. However, in the HPLC analysis we identified several hydroxyphenantrene metabolites that were detected at relatively high concentrations in all of the workers' urine samples. We could not separate 2- and 3-hydroxyphenanthrene (2?+?3-OH-Phe) in peak 1, and peak 2 contained both 1- and 9-hydroxyphenanthrene (1?+?9-OH-Phe). The phenanthrene metabolites were mainly conjugated to glucuronic acid and sulfate. There was a significant correlation between the 1-hydroxypyrene concentration and 2?+?3-OH-Phe (r?=?0.73) and 1?+?9-OH-Phe (r?=?0.64) in the urine samples. 1-Hydroxypyrene was measured in all post-shift urine samples but was not significantly correlated with workplace pyrene exposure, indicating that skin exposure is an important route of pyrene exposure in this factory. As with 1-hydroxypyrene, dermal PAH uptake may also account for the poor correlation between 2?+?3- and 1?+?9-OH-Phe and ambient phenanthrene. Discussion: Since dermal uptake is likely to be important in occupational PAH exposure in addition to inhalation, estimation of total PAH exposure is best achieved by quantitation of PAHs excreted into body fluids. However, it remains unclear whether there might be a difference in uptake and urinary excretion of 3-ring, 4-ring, or 5-ring PAHs and in the correlation between these metabolites and ambient-air PAH measurements. In summary, using immunaffinity chromatography, we did not find detectable amounts of B[a]P-tetrol in urine from workers occupationally exposed to PAH. However, by an HPLC/immunoaffinity method, relatively high amounts of 1-hydroxypyrene as well as 2?+?3- and 1?+?9-OH-Phe were quantitated in the urine samples, both of which are relevant as biomarkers of PAH exposure. 相似文献
76.
A. Newman-Tancredi D. Cussac V. Audinot M. J. Millan 《Naunyn-Schmiedeberg's archives of pharmacology》1999,359(6):447-453
Roxindole is a potential antidepressant agent. The present study determined its affinity and agonist efficacy at recombinant
human (h) dopamine hD2, hD3 and hD4 and serotonin (5-HT) h5-HT1A, h5-HT1B and h5-HT1D receptors. Roxindole exhibited high affinity at hD3 as well as at hD2 (short isoform) and hD4 (4-repeat isoform) receptors (pK
i values 8.93, 8.55 and 8.23, respectively). Further, it displayed high affinity at h5-HT1A receptors (pK
i = 9.42) but modest affinity at 5-HT1B and 5-HT1D receptors (pK
i values 6.00 and 7.05, respectively). In [35S]GTPγS binding experiments, roxindole was >20-fold more potent in stimulating [35S]GTPγS binding at hD3 than at hD2 or hD4 receptors (pEC50 = 9.23 vs. 7.88 and 7.69). However, whereas roxindole exhibited partial agonist activity at hD3 and hD4 sites (E
max = 30.0% and 35.1%, respectively, relative to dopamine = 100%), it only weakly activated hD2 receptors (E
max = 10.5%). Roxindole potently blocked dopamine-stimulated [35S]GTPγS binding at hD2 receptors (pK
B = 9.05). In comparison, the dopamine receptor agonist, (-)quinpirole, acted as a partial agonist at hD3 and hD4 sites (E
max = 67.4% and 66.3%, respectively) but surpassed the efficacy of dopamine at hD2 receptors (E
max = 132%). At h5-HT1A receptors, roxindole behaved as a high affinity (pK
i = 9.42) partial agonist (E
max = 59.6%, relative to 5-HT = 100%), whereas (-)quinpirole had negligible activity. The selective 5-HT1A antagonist, WAY 100,635, blocked roxindole (100 nM)-stimulated [35S]GTPγS binding at h5-HT1A receptors in a concentration-dependent manner (pK
B = 9.28). Roxindole only weakly stimulated [35S]GTPγS binding at 5-HT1B and 5-HT1D receptors (E
max = 27.1% and 13.7%). The present data suggest that roxindole activates mainly D3 vs. D2 or D4 receptors and 5-HT1A vs. 5-HT1B or 5-HT1D receptors. Activation of D3 and/or 5-HT1A receptors may thus contribute to its potential antidepressant properties.
Received: 4 February 1999 / Accepted: 29 March 1999 相似文献
77.
The augmentation effect of (–)pindolol as used in combination with SSRI to treat major depression has been ascribed to blocking
of dorsal raphe nucleus cell body 5-HT autoreceptors. In this study, the radioligand [carbonyl-11C]WAY-100635 and positron emission tomography were used to establish whether pindolol at a clinical dose level (10 mg s.o.d.)
occupies 5-HT1A receptors in the human brain in vivo. Three healthy males were recruited and each subject was used as his own control. The
5-HT1A receptor occupancy was calculated for the frontal and temporal cortex and the raphe nuclei, using and a ratio analysis with
the cerebellar cortex as the reference region. Maximal pindolol plasma concentration was reached within 3 h after drug administration.
Two hours after pindolol administration, the regional 5-HT1A receptor occupancy was within the range 7–21% in the three subjects. The study confirms that the 5-HT1A-receptor may be a clinically significant target for pindolol.
Received: 8 March 1999 / Final version: 15 March 1999 相似文献
78.
Rationale: Late onset type 1 alcoholism has been suggested to be associated with an underlying dopaminergic defect. Therefore, it is
relevant to study both postsynaptic D2-receptor and presynaptic dopamine transporter (DAT) densities among alcoholics. Objective: We investigated DAT densities, along with striatal and extrastriatal dopamine D2-receptor densities, in nine non-violent late-onset male alcoholics, who had no major mental disorder nor antisocial personality
disorder (ASPD), and nine healthy controls. Methods: [123I]PE2I and [123I]epidepride were used in SPECT imaging. Results: DAT occupancy ratios (striatum/cerebellum) were significantly lower among alcoholics than in controls. Extrastriatal D2-receptor occupancy ratios (temporal pole/cerebellum) were not significantly different between the groups. Conclusions: Striatal presynaptic DAT densities are decreased among type 1 alcoholics, and this finding is not associated with recent
alcohol abuse.
Received: 22 March 1999 / Final version: 25 June 1999 相似文献
79.
The temperature dependence of [35S]-t- butylbicyclophosphorothionate (TBPS) binding to the convulsant sites of the GABAA receptor complex was studied in membrane preparations of rat forebrain. Although specific [35S]TBPS binding was maximal around 20° C, the rate constants of dissociation decreased monotonously between 37°C and 2° C. The displacing potencies of the convulsant S(+) enantiomer of 1-methyl-5-phenyl-5-propyl-barbituric acid (MPPB) (IC50 = 1250 ± 30 M) and the depressant R(–) MPPB (IC5O = 310 ± 5 M) did not show significant changes between 19° C and 37° C. Therefore barbiturate binding seems to be driven by entropic, rather than enthalpic changes. An excess of MPPB enantiomers elicited accelerated and polyphasic dissociations of [35S]TBPS as compared to the monophasic dissociation by TBPS. Arrhenius analysis was applied to the measurable initial rate constants of dissociation. Arrhenius plots were linear between 2° C and 37° C. Activation parameters were similar when [35S] TBPS dissociation was triggered by the convulsants TBPS and S(+) MPPB. It can be attributed to similar conformations of the closed ionophore complex. In contrast, the depressant R(–) MPPB strongly decreased the activation energy of TBPS dissociation from the open ionophore ternary complex.In whole-cell patch-clamp experiments R(–) MPPB, but not S(+) MPPB, elicited chloride currents in rat primary cortical cultures with an EC50 value of 560 ± 30 M and a Hill coefficient of 2.9 ± 0.2. These currents were similar to those elicited by GABA and blocked by TBPS. A kinetic scheme is proposed for the dissociation of TBPS and to explain the different effects of MPPB enantiomers. Submillimolar R(–) MPPB is supposed to bind to (about three) barbiturate sites on GABAA-ionophores and to open them in a cooperative manner to result in a decreased activation energy for accelerated displacement of convulsant binding. 相似文献
80.
G. Olmos R. Alemany J. A. García-Sevilla 《Naunyn-Schmiedeberg's archives of pharmacology》1996,354(6):709-716
I2-imidazoline receptors labelled with [3H]-idazoxan in the rabbit and rat brains displayed high and low affinity, respectively, for the guanidide amiloride; reinforcing the previous definition of I2A-imidazoline receptors expressed in the rabbit brain and Its-imidazoline receptors expressed in the rat brain. Other drugs tested displayed biphasic curves in competition experiments, indicating the existence of high and low affinity sites for both subtypes of I2-imidazoline receptors. Among the drugs studied, bromoxidine, moxonidine, (+)- and (-)-medetomidine and clorgyline were more potent on the high and/or low affinity sites of 12B- than on their corresponding of I2A-imida-zoline receptors (K
iH
ratios 20 to 65). No correlation was found for the potencies of the drugs tested at the low affinity sites of both I2-imidazoline receptor subtypes. Preincubation (30 min at 25°°C) with 10-6 M clorgyline reduced by 60% the B
max of [3H]-idazoxan binding to I2 B-imidazoline receptors in the rat brain, but it did not affect the binding parameters of the radioligand saturation curves to I2A-imidazoline receptors in the rabbit brain. These results indicated that I2A- and I2B-imidazoline receptor subtypes differ in the pharmacological profiles of their high and low affinity sites and in the ability to irreversibly bind clorgyline. In rat cortical membranes western blot detection of immunoreactive imidazoline receptor proteins revealed a double band of 29/30 kDa and two less intense bands of 45 and 66 kDa. In rabbit cortical membranes the antibody used detected proteins of 30, 57 and 66 kDa. It is suggested that different imidazoline receptor proteins (45 vs 57 kDa) may account for the different pharmacological profiles of I2-imidazoline receptor subtypes. 相似文献