全文获取类型
收费全文 | 9068篇 |
免费 | 576篇 |
国内免费 | 44篇 |
专业分类
耳鼻咽喉 | 105篇 |
儿科学 | 320篇 |
妇产科学 | 288篇 |
基础医学 | 881篇 |
口腔科学 | 331篇 |
临床医学 | 830篇 |
内科学 | 2039篇 |
皮肤病学 | 276篇 |
神经病学 | 703篇 |
特种医学 | 332篇 |
外科学 | 1614篇 |
综合类 | 123篇 |
一般理论 | 7篇 |
预防医学 | 529篇 |
眼科学 | 251篇 |
药学 | 544篇 |
中国医学 | 40篇 |
肿瘤学 | 475篇 |
出版年
2024年 | 10篇 |
2023年 | 108篇 |
2022年 | 104篇 |
2021年 | 440篇 |
2020年 | 292篇 |
2019年 | 389篇 |
2018年 | 394篇 |
2017年 | 291篇 |
2016年 | 304篇 |
2015年 | 301篇 |
2014年 | 439篇 |
2013年 | 472篇 |
2012年 | 798篇 |
2011年 | 771篇 |
2010年 | 458篇 |
2009年 | 382篇 |
2008年 | 555篇 |
2007年 | 555篇 |
2006年 | 448篇 |
2005年 | 409篇 |
2004年 | 359篇 |
2003年 | 334篇 |
2002年 | 282篇 |
2001年 | 93篇 |
2000年 | 78篇 |
1999年 | 71篇 |
1998年 | 45篇 |
1997年 | 44篇 |
1996年 | 37篇 |
1995年 | 26篇 |
1994年 | 24篇 |
1993年 | 28篇 |
1992年 | 22篇 |
1991年 | 34篇 |
1990年 | 31篇 |
1989年 | 16篇 |
1988年 | 25篇 |
1987年 | 24篇 |
1986年 | 19篇 |
1985年 | 29篇 |
1984年 | 27篇 |
1983年 | 16篇 |
1982年 | 13篇 |
1981年 | 14篇 |
1980年 | 11篇 |
1979年 | 10篇 |
1978年 | 12篇 |
1977年 | 7篇 |
1974年 | 7篇 |
1973年 | 5篇 |
排序方式: 共有9688条查询结果,搜索用时 17 毫秒
61.
Estrogen increases intracellular p26Bcl-2 to p21Bax ratios and inhibits taxol-induced apoptosis of human breast cancer MCF-7 cells 总被引:7,自引:0,他引:7
Yue Huang Swapan Ray John C. Reed Ana Maria Ibrado Caroline Tang Amir Nawabi Kapil Bhalla 《Breast cancer research and treatment》1997,42(1):73-81
Recent studies have demonstrated that following estrogen ablation, estrogen responsive breast cancer cells undergo apoptosis. In addition, estrogen receptor (ER) expression has been strongly correlated with the expression of the bcl-2 gene product, p26Bcl-2 protein, which is known to inhibit apoptosis. In the present studies, we investigated whether estrogen affects the intracellular levels of p26Bcl-2 and thereby modulates taxol-induced apoptosis of estrogen responsive human breast cancer MCF-7 cells. Transfer of MCF-7 cells to a culture-medium without estrogens reduced their intracellular p26Bcl-2 levels by 50%. Inclusion of 0.1 M estradiol in the medium produced approximately a four-fold increase in p26Bcl-2, but not p29Bcl-xL or p21Bax levels; the expression of the c-myc and mdr-1 genes remained unchanged. Estradiol-induced four-fold increase in the ratio of the p26Bcl-2 to p21Bax levels caused a significant decline in the lethal, kilobase size DNA fragments of apoptosis, which had resulted when MCF-7 cells were cultured in a medium without estrogen. In addition, in MCF-7 cells, estradiol-induced increase in the intracellular p26Bcl-2 to p21Bax ratios was associated with a significant reduction in the large-sized DNA fragmentation induced by treatment with taxol. The increased ratios also protected MCF-7 cells against taxol-mediated cytotoxicity as assessed by the MTT assay. These results suggest that by modulating p26Bcl-2 levels, estrogens may affect the antitumor activity of taxol and potentially of other anti-breast cancer drugs against estrogen responsive human breast cancer cells. 相似文献
62.
There are no guidelines to help psychiatric researchers statistically adjust for missing data. We discuss the problems resulting from missing values, and illustrate some of them with examples from our work. Using structured instruments, we obtained clinical information from 241 patients. Some instrument items were not rated, and these did not occur randomly: hallucinations and delusions were most frequently unrated, especially in chronic schizophrenics, and patients with high scores for other psychopathology. Systematically assigning an intermediate value between present and absent to nonrated items was a satisfactory solution, unaffected by nonrandom missing values. This simple solution was equivalent to a complicated one (vectoring) in discriminating patients. When relationships between variables are linear, we recommend the intermediate value method as a practical solution to missing values. We stress that missing values do not mean missing information, and the most common response to missing values (dropping subjects) is least informative. 相似文献
63.
J. Amir M. D. Liora Harel M. D. Tal Eidlitz-Markus M. D. I. Varsano M. D. 《Infection》1995,23(6):389-390
Summary Toxocariasis in children is usually an asymptomatic infection and those with clinical illness have non-specific systemic or local manifestations. We present a 24-month-old boy with bilateral lymphedema of the feet as the main clinical manifestation of toxocariasis. The child presented with limping and nonpitting edema of both feet. Laboratory investigation revealed leucocytosis of <20,000/mm3 with a differential count of <50% eosinophils. No other cause of edema was found. The ELISA for toxocariasis revealed a high titer of 1:4,096. The limping and the lymphedema disappeared during the third week of his illness. We suggest that toxocariasis should be considered as a possible cause of lymphedema and eosinophilia in young children.Zusammenfassung Die Toxocariasis nimmt bei Kindern in der Regel einen asymptomatischen Verlauf. Wenn Krankheitszeichen auftreten, handelt es sich um unspezifische Allgemeinsymptome oder lokale Symptome. Wir berichten über einen 24 Monate alten Jungen, bei dem ein bilaterales Lymphödem der Füße die Hauptmanifestation der Toxocariasis war. Das Kind hinkte und hatte an beiden Füßen ein nicht dellenbildendes Ödem. Dabei bestand eine Leukozytose von >20 000/mm3 mit >50% Eosinophilen im Differentialblutbild. Andere Ursachen für das Ödem waren nicht zu finden. Der ELISA für Toxocariasis ergab einen hohen Titer von >1:4 096. Hinken und Lymphödem verschwanden im Verlauf von drei Wochen. Wir verweisen auf die Möglichkeit einer Toxocariasis als mögliche Ursache für Lymphödem und Eosinophilie bei kleinen Kindern.
Lymphödem als Primärsymptom einer Toxocariasis相似文献
64.
Arezo Nahavandi Ahmad Reza Dehpour Ali Reza Mani Homayoun Homayounfar Ali Abdoli 《European journal of pharmacology》1999,370(3):1170
In this study the effect of nitric oxide (NO) synthesis inhibition on ethanol-induced gastric damage was evaluated in bile duct-ligated, sham-operated and unoperated rats. The animals were injected intraperitoneally with saline,
-arginine (200 mg/kg) or NG-nitro-
-arginine methylester (
-NAME) in doses of 5, 15 and 30 mg/kg, 30 min before ethanol administration. The animals were killed 1 h after ethanol administration and their stomachs were removed for measurement of gastric mucosal damage. The results showed that
-NAME significantly enhanced the development of gastric mucosal lesions in sham-operated and unoperated rats, while in bile duct-ligated animals,
-NAME decreased and
-arginine enhanced the potentiation of ethanol-induced gastric mucosal damage. The plasma level of nitrite and nitrate was also measured and was significantly higher in bile duct-ligated rats than in control groups. The results suggest that inhibition of NO synthase with
-NAME has different effects on ethanol-induced gastric damage in cholestatic groups and in normal rats and that these effects can be explained by overproduction of NO in bile duct-ligated animals. 相似文献
65.
Tizabi Y Overstreet DH Rezvani AH Louis VA Clark E Janowsky DS Kling MA 《Psychopharmacology》1999,142(2):193-199
Epidemiological studies indicate a high incidence of cigarette smoking among depressed individuals. Moreover, individuals
with a history of depression have a much harder time giving up smoking. It has been postulated that smoking may reflect an
attempt at self-medication with nicotine by these individuals. Although some animal and human studies suggest that nicotine
may act as an antidepressant, further verification of this hypothesis and involvement of nicotinic cholinergic system in depressive
symptoms is required. Flinders Sensitive Line (FSL) rats have been proposed as an animal model of depression. These rats,
selectively bred for their hyperresponsiveness to cholinergic stimulation, show an exaggerated immobility in the forced swim
test compared to their control Flinders Resistant Line (FRL) rats. Acute or chronic (14 days) administration of nicotine (0.4 mg/kg
SC) significantly improved the performance of the FSL but not the FRL rats in the swim test. The effects of nicotine on swim
test were dissociable from its effects on locomotor activity. Moreover, the FSL rats had significantly higher [3H]cytisine binding (selective for the α4β2 nicotinic receptor subtype) but not [125I]alpha-bungarotoxin binding (selective for the α7 subtype) in the frontal cortex, striatum, midbrain and colliculi compared to FRL rats. These data strongly implicate the
involvement of central nicotinic receptors in the depressive characteristics of the FSL rats, and suggest that nicotinic agonists
may have therapeutic benefits in depressive disorders.
Received: 9 June 1998/Final version: 6 August 1998 相似文献
66.
Joel M. Childers MD Amir Nasseri MD Earl A. Surwit MD 《American journal of obstetrics and gynecology》1996,175(6):1451-1459
OBJECTIVE: Our aim was to evaluate the feasibility and applicability of operative laparoscopy in the management of adnexal masses that do not meet the standard serum CA 125 and ultrasonographic criteria for benignity. STUDY DESIGN: One hundred thirty-eight patients underwent operative laparoscopy for removal of suspicious adnexal masses. The CA 125 level was >35 mIU/ml in 39 of 138 (28%) patients; ultrasonographic findings were abnormal in 127 of 138 (92%); masses were >10 cm in 43 of 138 (32%) of patients. RESULTS: Malignancies were discovered in 14% (19/138) of patients. Eight percent (11/138) of the procedures were converted to laparotomy, six because of inability to dissect the mass laparoscopically and five for staging or debulking of carcinoma. Operative times ranged from 25 to 210 minutes, with a mean of 86. Three major complications were encountered-an enterotomy and a lacerated vena cava, both of which were repaired laparoscopically, and a small bowel herniation through a lateral port site that required reoperation. Hospital stays ranged from 0 to 11 days, with a mean of 1.5. In two patients with "apparent" stage I adnexal carcinomas recurrence was diagnosed 6 and 38 months after surgery. CONCLUSIONS: Laparoscopic management of suspicious adnexal masses is technically feasible, with a low rate of morbidity and a short hospital stay. Adnexal carcinomas can be identified and managed appropriately with staging and complete resection as indicated. (Am J Obstet Gynecol 1996;175:1451-9.) 相似文献
67.
Adrian L. Harris Huatang Zhang Amir Moghaddam Steve Fox Prudence Scott Adam Pattison Kevin Gatter Ian Stratford Roy Bicknell 《Breast cancer research and treatment》1996,38(1):97-108
Summary Several groups have shown that quantitation of tumor angiogenesis by counting blood vessels in primary breast cancer gives an independent assessment of prognosis. Poor prognosis is associated with high blood vessel counts. We have shown that the rate of cell division in endothelial cells is much higher in breast tumours than in normal breast. Breast cancer cell lines and primary human breast tumours express a wide range of vascular growth factors, including VEGF, placenta growth factor, pleiotrophin, TGF1, acidic and basic FGF, and platelet-derived endothelial cell growth factor. Inhibiting angiogenesis by blocking vascular growth factors would be difficult with highly specific agents, but drugs with a broader spectrum of antagonism may be effective. We have developed several suramin analogues which are less toxic than suraminin vivo but more potent in inhibiting angiogenesis, and these have been developed for Phase I. A combination of anti-angiogenesis agents with drugs activated by hypoxia may also be useful, because anti-angiogenesis alone may not kill cells, whereas activation of hypoxic drugs could synergize.New endpoints may be necessary because inhibition of new blood vessel formation may not cause tumour regression. Thus, the endpoint of stable disease and biochemical assessment of inhibition of angiogenesis may be much more important in therapeutic studies and for drug development in the future. The prognostic importance of angiogenesis suggests that this should be a major new therapeutic target.Presented at the symposium "New Approaches in the Therapy of Breast Cancer", Georgetown University Medical Center, Washington DC, October 1994, generously supported by an education grant from Bristol-Myers Squibb. 相似文献
68.
The present study investigated the temporal structure of sleep propensity during 48 hours using an ultrashort 7-min sleep/13-min wake cycle. Eight subjects were tested under two experimental conditions of either attempting sleep, or resisting sleep after a monitored night in the laboratory. Electrophysiological recordings were carried out during the 7-min trials. The temporal structure and the overall level of sleepiness of the 48-hour sleep propensity functions calculated from the amount of total sleep in each trial revealed a high within-subjects stability. This was found both across the two days of the study within conditions, and across conditions. Also, diurnal levels of sleepiness were systematically related to nocturnal sleep parameters. Subjects having short nocturnal sleep latencies and higher sleep efficiencies slept more during the day. It is proposed that the structure and level of the sleep propensity function can be used to characterize individuals along two dimensions of somnotypology: "morningness-eveningness" and "sleepy-alert." 相似文献
69.
Muhammad Jamshaid Samia Yousuf Nadeem Irfan Bukhari Amir Ali Rizvi 《European journal of drug metabolism and pharmacokinetics》2003,28(1):1-6
Three commercially available brands of amikacin were investigated in a parallel study design for the assessment of comparative pharmacokinetics in pediatric oncology patients with chemotherapy-induced neutropenic febrile episode. Amikacin concentration in serum samples was determined by fluorescence polarization immunoassay method using Abbott TDx system. Computer software, PK II was used for computation of pharmacokinetic parameters of amikacin. The serum concentration of all brands nonsignificantly (p > 0.05) varied at all time points, except at 1 and 2 hrs post dosing. At 1 hr post dosing, the serum concentration of brand II varied from rest of two brands. Whereas at 2 hr following I/V infusion, brands II and I were statistically different. Highest serum concentration of 38.69 +/- 1.45 microg/ml was observed in case of brand III while brands I and II showed lower but not significantly different serum concentration values, i.e., 36.30 +/- 1.65 and 37.89 +/- 1.32 microg/ml, respectively when compared with brand I. The other pharmacokinetic parameters of 3 brands found to have non-significant difference (P < 0.05) except, t(1/2)alpha and Cl of brands I and II that deviated statistically significant (p < 0.01). The relative bioavailability of brand II and III as compared with brand I, considered as standard 86.17 and 96.86%, respectively falls within the accepted limits of +/- 20% required for the bioequivalence of any two brands. Based upon findings of the present study, all these brands may be used interchangeably in oncology patients. Further studies, however are needed to determine whether the statistically elevated Cl value in brand II is of any clinical significance. 相似文献
70.
Dina Chelouche Lev Amir Onn Vladislava O Melinkova Claudia Miller Valerie Stone Maribelis Ruiz Eric C McGary Honnavara N Ananthaswamy Janet E Price Menashe Bar-Eli 《Journal of clinical oncology》2004,22(11):2092-2100
PURPOSE: In recent years, the incidence of cutaneous melanoma has increased more than that of any other cancer. Dacarbazine is considered the gold standard for treatment, having a response rate of 15% to 20%, but most responses are not sustained. Previously, we have shown that short exposure of primary cutaneous melanoma cells to dacarbazine resulted in the upregulation of interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF). The purpose of the present study was to determine how long-term exposure of melanoma cells to dacarbazine would affect their tumorigenic and metastatic potential in vivo. MATERIALS AND METHODS: The primary cutaneous melanoma cell lines SB2 and MeWo were repeatedly exposed in vitro to increasing concentrations of dacarbazine, and dacarbazine-resistant cell lines SB2-D and MeWo-D were selected and examined for their ability to grow and metastasize in nude mice. RESULTS: The dacarbazine-resistant cell lines SB2-D and MeWo-D exhibited increased tumor growth and metastatic behavior in vivo. This increase could be explained by the activation of RAF, MEK, and ERK, which led to the upregulation of IL-8 and VEGF. More IL-8, VEGF, matrix metalloproteinase-2 (MMP-2), and microvessel density (CD-31) were found in tumors produced by SB2-D and MeWo-D in vivo than in those produced by their parental counterparts. No mutations were observed in BRAF. CONCLUSION: Our results have significant clinical implications. Treatment of melanoma patients with dacarbazine could select for a more aggressive melanoma phenotype. We propose that combination treatment with anti-VEGF/IL-8 or MEK inhibitors may potentiate the therapeutic effects of dacarbazine. 相似文献