全文获取类型
收费全文 | 7682篇 |
免费 | 548篇 |
国内免费 | 47篇 |
专业分类
耳鼻咽喉 | 141篇 |
儿科学 | 92篇 |
妇产科学 | 120篇 |
基础医学 | 1179篇 |
口腔科学 | 224篇 |
临床医学 | 738篇 |
内科学 | 2238篇 |
皮肤病学 | 118篇 |
神经病学 | 558篇 |
特种医学 | 228篇 |
外科学 | 992篇 |
综合类 | 61篇 |
一般理论 | 2篇 |
预防医学 | 272篇 |
眼科学 | 132篇 |
药学 | 600篇 |
1篇 | |
中国医学 | 21篇 |
肿瘤学 | 560篇 |
出版年
2023年 | 31篇 |
2022年 | 47篇 |
2021年 | 105篇 |
2020年 | 66篇 |
2019年 | 97篇 |
2018年 | 113篇 |
2017年 | 100篇 |
2016年 | 129篇 |
2015年 | 155篇 |
2014年 | 219篇 |
2013年 | 242篇 |
2012年 | 418篇 |
2011年 | 464篇 |
2010年 | 258篇 |
2009年 | 247篇 |
2008年 | 417篇 |
2007年 | 419篇 |
2006年 | 500篇 |
2005年 | 465篇 |
2004年 | 454篇 |
2003年 | 374篇 |
2002年 | 399篇 |
2001年 | 216篇 |
2000年 | 207篇 |
1999年 | 163篇 |
1998年 | 119篇 |
1997年 | 79篇 |
1996年 | 62篇 |
1995年 | 74篇 |
1994年 | 65篇 |
1993年 | 69篇 |
1992年 | 115篇 |
1991年 | 98篇 |
1990年 | 110篇 |
1989年 | 94篇 |
1988年 | 81篇 |
1987年 | 81篇 |
1986年 | 80篇 |
1985年 | 74篇 |
1984年 | 56篇 |
1983年 | 60篇 |
1982年 | 46篇 |
1981年 | 34篇 |
1979年 | 57篇 |
1978年 | 34篇 |
1977年 | 36篇 |
1976年 | 39篇 |
1975年 | 36篇 |
1974年 | 38篇 |
1973年 | 38篇 |
排序方式: 共有8277条查询结果,搜索用时 15 毫秒
71.
Because both Rhodamine 123 (R123) and hyperthermia have been shown to be cytotoxic, we examined their effect, independently and in combination, on five different human malignant cell lines in vitro and on cultured melanoma cells grown intradermally in nude mice. The cell lines examined include two human melanomas, UCLA-SO-M14 and UCLA-SO-M21, the colon cancer cell line HT29, the human lung cancer cell line P3, and the human breast cancer cell line B231. R123 and hyperthermia, when used in combination, were found to be cytotoxic for these five different human malignant cell lines in vitro. The two agents together appear to enhance the cytotoxic effect of each alone, as documented by synergistic ratios ranging from 2.31 to 45 for the different cell lines. In the "nude" mouse model, animals were treated with a combination of R123 and hyperthermia (43 degrees C for 90 min). A statistically significant (P = 0.04) decrease in tumor growth rate was observed when compared with the rate of tumor growth in untreated animals. The results suggest a potential role for R123 in combination with hyperthermia in the treatment of malignant cells. 相似文献
72.
Fabian F Moebius Raphael J Reiter Markus Hanner Hartmut Glossmann 《British journal of pharmacology》1997,121(1):1-6
- The sigma-drug binding site of guinea-pig liver is carried by a protein which shares significant amino acid sequence similarities with the yeast sterol C8–C7 isomerase (ERG2 protein). Pharmacologically - but not structurally - the sigma1-site is also related to the emopamil binding protein, the mammalian sterol C8–C7 isomerase. We therefore investigated if sterol C8–C7 isomerase inhibitors are high affinity ligands for the (+)-[3H]-pentazocine labelled sigma1-binding site.
- Among the compounds which bound with high affinity to native hepatic and cerebral as well as to yeast expressed sigma1-binding sites were the agricultural fungicide fenpropimorph (Ki 0.005 nM), the antihypocholesterinaemic drugs triparanol (Ki 7.0 nM), AY-9944 (Ki 0.46 nM) and MDL28,815 (Ki 0.16 nM), the enantiomers of the ovulation inducer clomiphene (Ki 5.5 and 12 nM, respectively) and the antioestrogene tamoxifen (Ki 26 nM).
- Except for tamoxifen these affinities are essentially identical with those for the [3H]-ifenprodil labelled sterol C8–C7 isomerase of S. cerevisiae. This demonstrates that sigma1-binding protein and yeast isomerase are not only structurally but also pharmacologically related. Because of its affiliations with yeast and mammalian sterol isomerases we propose that the sigma1-binding site is localized on a sterol isomerase related protein, involved in postsqualene sterol biosynthesis.
73.
Joseli Lannes-Vieira Jochen Gehrmann Georg W. Kreutzberg Hartmut Wekerle 《Acta neuropathologica》1994,87(5):435-442
We have investigated the T cell receptor (TCR) repertoire in the inflammatory infiltrates of T line-transferred experimental autoimmune encephalomyelitis (EAE) of the Lewis rats. Using a panel of TCR V-specific monoclonal antibodies (mAbs) and immunocytochemistry, we studied the nature of the T cells entering the central nervous system (CNS) after transfer of either myelin basic protein (MBP)-reactive, or MBP-reactive but non-encephalitogenic T cell lines. All the MBP-specific T cell lines predominantely used the V8.2 TCR chain. T cell lines specific for the tuberculin purified protein derivative (PPD), using TCR V genes different from V8.2, served as controls. We first studied the time course of T cells entering the CNS. In all recipient rats, small, but significant numbers of -TCR-expressing infiltrate cells appeared in the CNS within the first 24 h after T cell transfer. In animals injected with either type of MBP-reactive T cells, the early infiltrate cells were preferentially located within the parenchyma of the spinal cord, while in PPD T lineinjected rats, the lymphocytes were mostly found in the meninges. TCR V gene usage was examined on the peak of clinical disease. Six days after T cell transfer, the TCR repertoire used by infiltrating lymphocytes in general seemed to be highly diverse. None of the V isotypes examined (i.e. V8.2, V8.5 or V10) was used by a major population of the -TCR-positive T cells. A more detailed, quantitative analysis of individual infiltrate compartments revealed, however, a preferential accumulation of V8.2-positive T cells within the parenchyma. In contrast, perivascular infiltrating cells used V genes randomly. Our results confirm first that activated T lymphocytes enter the brain rapidly irrespective of their antigen specificity. Second, the data show that most of the perivascular infiltrate T cells in the acute EAE lesion are host-derived, recruited presumably from the recirculating T cell pool, while the encephalitogenic, V8.2-positive T cells preferentially persist within the parenchyma.Abbreviations
EAE
experimental autoimmune encephalomyelitis
-
MBP
myelin basic protein
-
TCL
T cell line
Supported by the Brazilian Research Council (CNPq) 相似文献
74.
Bernd Mühlbauer Erik Hartenburg Hartmut Osswald 《Naunyn-Schmiedeberg's archives of pharmacology》1994,349(3):244-249
Previously, we have found that feeding is a dominant factor controlling urinary dopamine excretion (UDA) in conscious rats (Mühlbauer and Osswald 1992). Since the renal response to feeding is also characterized by an increase in glomerular filtration rate (GFR), we wanted to investigate in a first step whether the feeding-induced elevations of GFR and UDA could be causally related phenomena. Therefore, we studied the influence of dopamine synthesis and dopamine receptor blockade on the renal response to amino acid infusion (AA) in thiopental anesthetized rats. AA infusion (n = 7) increased GFR by 33±7% (P<0.001) and UDA by 87±19% (P<0.001). In the presence of benserazide (BZD, n = 5), an inhibitor of dopamine synthesis, infused i.v. at a dose of 30 g/min/kg, UDA was suppressed to values below detection limit and the AA-induced GFR increase was abolished. Continuous intravenous infusion of the DA1 receptor antagonist SCH 23390 (SCH, n = 7) in a dose of 4.0 g/kg/min did not prevent the AA-induced increase in GFR (33±3%, P<0.001) and UDA (97±12%, P< 0.001). In contrast, S-sulpiride (SUL), a specific DA2 receptor antagonist, infused continuously i.v. in a dose of 5 g/kg/min, completely abolished the AA-induced GFR increase, while UDA was increased 1.6-fold (P<0.01). Like BZD, both dopamine receptor antagonists did not affect renal sodium excretion substantially.Our results suggest, that endogenous dopamine could act as a mediator in the renal response to amino acid infusion in the rat, most likely by activation of DA2 receptors.
Correspondence to:B. Mühlbauer at the above address 相似文献
75.
76.
Esa R. Korpi Garry Wong Hartmut Lüddens 《Naunyn-Schmiedeberg's archives of pharmacology》1995,352(4):365-373
Clozapine, an atypical neuroleptic, functionally antagonizes the -aminobutyric acid-induced chloride uptake via the main central inhibitory receptor, -aminobutyric acid type A (GABAA) receptor, in brain vesicles. GABAA antagonism by micromolar concentrations of clozapine is more efficient in rat cerebrocortical and hippocampal membranes than in cerebellar membranes, as evidenced by clozapine reversal GABA-inhibition of [35S]t-butylbicyclophosphorothionate ([35S]TBPS) binding. A typical neuroleptic, haloperidol, failed to antagonize GABA in any of these brain regions, while the specific GABAA antagonist 2-(3-carboxy-2,3-propyl)-3-amino-6-p-methoxyphenylpyrazinium bromide (SR 95531) was efficient in all three brain regions. Clozapine action on [35S]TBPS binding was unaffected by the benzodiazepine receptor antagonist flumazenil. Clozapine inhibited the binding of [3H]muscimol and [3H]SR 95531 to the GABA recognition site, but this effect only partially correlated with the regional differences in and the potency of clozapine antagonism of GABA-inhibition of [35S]TBPS binding, suggesting that also other than GABA sites may mediate clozapine actions. Autoradiography of [35S]TBPS binding revealed GABA antagonism by clozapine in most brain regions. Main exceptions were cerebellar granule cell and molecular layers, olfactory bulb external plexiform and glomerular layers and primary olfactory cortex, where clozapine antagonized GABA inhibition less than average, and lateral hypothalamic and preoptic areas where its antagonism was greater than average. Recombinant 622 receptors, the predominant 6 subunit-containing receptor subtype in cerebellar granule cells, failed to show GABA antagonism by clozapine up to 100 M. In contrast, recombinant 122 receptors, forming the predominant receptor subtype in the brain, were clozapine sensitive. Recombinant 622 and 632 receptors resulted in clozapine-insensitive receptors, whereas 612 receptors were clozapine sensitive. The efficacy of clozapine to antagonize GABA in 1x2 receptors decreased in the order of 112>122>132. The results indicate that clozapine antagonizes the function of most GABAA receptor subtypes, and that the interaction is determined by the interaction of the and subunit variants. GABA antagonism is a unique property of clozapine, not shared by haloperidol, which might be involved in the pharmacological mechanism for the increased seizure susceptibility associated with clozapine treatment. 相似文献
77.
BACKGROUND: Maximum lactate steady state (MLSS) is defined as the highest steady state exercise level one can maintain while also maintaining an equilibrium between the elimination of blood lactate and the diffusion of lactate into the blood. MLSS is an excellent tool for assessing fitness level, predicting endurance performance, and designing training programs. METHODS: This investigation assesses the validity of the Lactate Minimum Test (LMT), which consists of inducing lactic acidosis through a VO2peak test, followed by an eight-minute walking recovery and an incremental exercise test, to determine if the running velocity associated with the minimum lactate value predicts the MLSS velocity. Following this LMT, two constant velocity 28-minute runs were performed, one at the predicted MLSS velocity (trial 1) and the other 0.13 m sec-1 (4-8%) above the predicted MLSS velocity (trial 2). Ten active female subjects participated (32 +/- 7 yrs (mean +/- SD); 65.7 +/- 16.4 kg; VO2peak 40.0 +/- 7.5 ml.kg-1.min-1). RESULTS: During trial 1, there was a -0.6 +/- 0.3 mmol l-1 (mean +/- SE) change in lactate. Based on a definition of lactate steady state (LSS) as less than a 0.5 mmol.l-1 increase, this value signified LSS. A similar comparison during trial 2 revealed a 1.8 +/- 0.3 mmol.l-1 increase in lactate, signifying a workload above LSS and therefore confirming trial 1 as the maximum LSS (MLSS). CONCLUSIONS: These results suggest that the test protocol accurately predicted the MLSS velocity. 相似文献
78.
Summary It has been postulated long ago that “eloquent” areas shift their location in patients with arteriovenous malformations (AVM).
Obviously the “motor region” in not located in the precentral gyrus in a patient with an AVM in the “motor region”.
We report on the case of a 15-year old boy with an AVM in the left sensorimotor cortex, in whom intra-operative mapping showed
an inexcitability of the precentral gyrus, while stimulation of the cortex anterior to the primary motor cortex elicited motor
responses. This indicates that motor function was translocated from the primary to the supplementary motor cortex. Surgery
was performed under general anaesthesia. Neurophysiological monitoring was performed throughout surgery. The central sulcus
was identified by phase reversal of the somatosensory evoked potentials. The motor cortex was mapped by direct high-frequency
(500 Hz) monopolar anodal stimulation.
In the patient herein reported, stimulation of the “anatomically” defined primary motor cortex induced no motor response,
as expected. Motor response was elicited only by stimulation of the cortex anterior to the precentral gyrus. There was no
postoperative deterioration of motor function. These observations indicate that the precentral gyrus was functionally “useless”.
The motor region was relocated into more rostral areas in the supplementary motor cortex. This translocation of function in
the presence of an AVM indicates cerebral plasticity. 相似文献
79.
Central nervous system effects of intranasally administered insulin during euglycemia in men 总被引:5,自引:0,他引:5
Insulin receptors have been detected in several structures of the brain, yet the biological significance of insulin acting on the brain remains rather unclear. In humans, direct central nervous effects of insulin are difficult to distinguish from alterations in neuronal functions because of insulin-induced decrease in blood glucose levels. Since several intranasally administered viruses, peptides, and hormones have been shown to penetrate directly from the nose to the brain, we tested whether insulin after intranasal administration likewise has access to the brain. After a 60-min baseline period, insulin (20 IU H-Insulin 100 Hoechst) or vehicle (2.7 mg/ml m-Cresol) was intranasally administered every 15 min to 18 healthy subjects according to a double-blind within-subject crossover design. Auditory-evoked potentials (AEP) indexing cortical sensory processing were recorded while the subjects performed a vigilance task (oddball paradigm) during the baseline phase and after 60 min of intranasal treatment with insulin or placebo. Blood glucose and serum insulin levels were not affected by intranasal insulin. Compared with placebo, intranasal administration of insulin reduced amplitudes of the N1 (P < 0.005) and P3 (P < 0.02) components of the AEP and increased P3 latency (P < 0.05). The reduction in P3 amplitude was most pronounced over the frontal recording site (2.42 +/- 1.00 vs. 4.92 +/- 0.79 microV, P < 0.0005). At this site, after insulin administration, a broad negative shift developed in the AEP between 280 and 500 ms poststimulus (area under the curve -166.0 +/- 183.8 vs. 270.8 +/- 138.7 microV x ms after placebo, P < 0.01). The results suggest that after intranasal administration, insulin directly enters the brain and exerts distinct influences on central nervous functions in humans. 相似文献
80.
Noise has the potential to cause stress reactions. Chronic noise-induced stress accelerates the ageing of the myocardium and thus increase the risk of myocardial infarction. The involved pathomechanisms include acute increase of catecholamines or cortisol under acute noise exposure and an interaction between endocrine reactions and intracellular Ca/Mg shifts. Chronic noise exposure of animals on a diet with suboptimal magnesium content led to increase of connective tissue and calcium, and decrease of magnesium in the myocardium. These changes were correlated to noradrenaline and normal ageing. Post mortem studies of hearts from victims of ischemic heart diseases confirmed the importance of Ca/Mg shifts in humans. Recent epidemiological studies support the importance of noise as a risk factor in circulatory and heart diseases, especially in myocardial infarction. 相似文献