全文获取类型
收费全文 | 1373篇 |
免费 | 70篇 |
国内免费 | 20篇 |
专业分类
耳鼻咽喉 | 4篇 |
儿科学 | 24篇 |
妇产科学 | 10篇 |
基础医学 | 133篇 |
口腔科学 | 6篇 |
临床医学 | 100篇 |
内科学 | 359篇 |
皮肤病学 | 13篇 |
神经病学 | 76篇 |
特种医学 | 26篇 |
外科学 | 307篇 |
综合类 | 8篇 |
预防医学 | 51篇 |
眼科学 | 6篇 |
药学 | 85篇 |
中国医学 | 2篇 |
肿瘤学 | 253篇 |
出版年
2023年 | 13篇 |
2022年 | 28篇 |
2021年 | 53篇 |
2020年 | 15篇 |
2019年 | 23篇 |
2018年 | 25篇 |
2017年 | 22篇 |
2016年 | 45篇 |
2015年 | 30篇 |
2014年 | 46篇 |
2013年 | 50篇 |
2012年 | 102篇 |
2011年 | 121篇 |
2010年 | 53篇 |
2009年 | 49篇 |
2008年 | 83篇 |
2007年 | 88篇 |
2006年 | 73篇 |
2005年 | 76篇 |
2004年 | 82篇 |
2003年 | 81篇 |
2002年 | 65篇 |
2001年 | 12篇 |
2000年 | 16篇 |
1999年 | 26篇 |
1998年 | 15篇 |
1996年 | 10篇 |
1995年 | 13篇 |
1994年 | 12篇 |
1993年 | 6篇 |
1992年 | 12篇 |
1991年 | 18篇 |
1990年 | 16篇 |
1989年 | 8篇 |
1988年 | 4篇 |
1987年 | 8篇 |
1985年 | 11篇 |
1983年 | 4篇 |
1981年 | 3篇 |
1980年 | 5篇 |
1979年 | 5篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1975年 | 2篇 |
1972年 | 2篇 |
1970年 | 3篇 |
1969年 | 2篇 |
1968年 | 2篇 |
1967年 | 3篇 |
1966年 | 7篇 |
排序方式: 共有1463条查询结果,搜索用时 31 毫秒
11.
Differentiation of subtypes B and E of human immunodeficiency virus type 1 by polymerase chain reaction using novel env gene primers 总被引:2,自引:0,他引:2
Yagyu F Ikeda Y Ariyoshi K Sugiura W Wongkhomthong SA Masuda M Ushijima H 《Journal of virological methods》2002,101(1-2):11-20
Novel sets of env gene PCR primers for distinguishing human immunodeficiency virus type 1 (HIV-1) subtypes B and E were designed. These primers anneal to different regions of the env gene and amplify DNA fragments of distinct sizes in a subtype-specific manner. Blood samples from 11 HIV-1 carriers in Thailand and 46 carriers in Japan were examined by PCR. The new env primers detected HIV-1 proviral DNA in 100% (11/11) and 88% (37/42) of the subtype B and E infection cases, respectively. The env primers also detected proviral DNA in saliva and breast milk samples in seven of 11 cases and two of three cases, respectively. The PCR subtyping results matched completely with those obtained by nucleotide sequencing of the env V3 region. The results suggest that the PCR using the env primers designed in this study may be an accurate and cost-effective method for differentiating subtypes B and E of HIV-1 in a large number of clinical samples. However, subtype E specific primer cross-react with subtype A, C, G, the new primer in this study is useful for regions in South East Asia where subtype E is predominant. 相似文献
12.
Omasu F Ezura Y Kajita M Ishida R Kodaira M Yoshida H Suzuki T Hosoi T Inoue S Shiraki M Orimo H Emi M 《Journal of human genetics》2003,48(7):342-345
Twin and family studies had shown that genetic factors are important determinants of bone mass. Multiple genes might be involved.
One candidate gene, the reversion-induced LIM gene (RIL), is a PDZ and LIM-domain-containing protein and has been localized within the cytokine cluster of chromosome 5 (5q31.1).
In a genetic study of 370 adult Japanese women, we investigated the correlation between radial bone mineral density (BMD)
and a genetic variation (−3333T→C) of the 5'-flanking region of RIL gene. A significant association was identified between the RIL variation −3333T→C and radial BMD (r=0.15, P=0.003). The variation of the RIL locus may be an important determinant of osteoporosis. 相似文献
13.
Dominant-negative hypoxia-inducible factor-1 alpha reduces tumorigenicity of pancreatic cancer cells through the suppression of glucose metabolism 总被引:16,自引:0,他引:16 下载免费PDF全文
Chen J Zhao S Nakada K Kuge Y Tamaki N Okada F Wang J Shindo M Higashino F Takeda K Asaka M Katoh H Sugiyama T Hosokawa M Kobayashi M 《The American journal of pathology》2003,162(4):1283-1291
In the tumor cells exposed to hypoxia, hypoxia-inducible factor-1 (HIF-1)-mediated adaptation responses such as angiogenesis and anaerobic metabolism are induced for their survival. We have recently reported that the constitutive expression of HIF-1 alpha renders pancreatic cancer cells resistant to apoptosis induced by hypoxia and glucose deprivation. We then established dominant-negative HIF-1 alpha (dnHIF-1 alpha) transfectants and examined their susceptibility to apoptosis and growth inhibition induced by hypoxia and glucose deprivation in vitro and their tumorigenicity in SCID mice. We further examined the expressions of aldolase A and Glut-1 in vitro and Glut-1 expression and glucose uptake in the tumor tissues and microvessel counts in the tumor tissues. As a result, dnHIF-1 alpha rendered the pancreatic cancer cells sensitive to apoptosis and growth inhibition induced by hypoxia and glucose deprivation. Also it abrogated the enhanced expression of Glut-1 and aldolase A mRNAs under hypoxia and reduced the expression of Glut-1 and the glucose uptake in the tumor tissues and consequently in vivo tumorigenicity. We found no significant difference in the microvessel counts among the tumor tissues. From these results, we suggest that the disruption of the HIF-1 pathway might be effective in the treatment of pancreatic cancers. 相似文献
14.
Hagiwara K Nakagawasai O Murata A Yamadera F Miyoshi I Tan-No K Tadano T Yanagisawa T Iijima T Murakami M 《Neuroscience research》2003,46(4):493-497
We investigated the relationship between the antinociceptive effect of the opiate agonist loperamide at the spinal level and its inhibitory effect on calcium influx. Intrathecal administration of loperamide showed a significant antinociceptive effect in the formalin test, which was not prevented by naloxone. On the other hand, no significant effects were observed by nicardipine, an L-type specific blocker, or by BAY K8644, an L-type specific agonist, suggesting no significant role of L-type calcium channels in nociceptive signal transduction. Loperamide suppressed the calcium influx in dorsal root ganglion neurons. As the antinociceptive effect of loperamide was not affected by naloxone or other calcium channel blocking toxins, and loperamide showed a direct inhibitory effect on calcium-influx, the analgesic effect of intrathecally injected loperamide might be due to its blockade of the voltage-dependent calcium channels at the terminals of the primary afferent fibers. 相似文献
15.
Keisuke Yoshihama Hideki Mutai Mariko Sekimizu Fumihiro Ito Shin Saito Shintaro Nakamura Takuya Mikoshiba Ryoto Nagai Akiko Takebayashi Fuyuki Miya Kenjiro Kosaki Hiroyuki Ozawa Tatsuo Matsunaga 《Clinical genetics》2023,103(4):466-471
Carotid body tumor (CBT) is classified as a paraganglioma (PGL). Here, we report the genetic background, protein expression pattern, and clinical findings of 30 Japanese CBT cases. Germline pathogenic or likely pathogenic (P/LP) variants of genes encoding succinate dehydrogenase subunits (SDHs) were detected in 15 of 30 cases (50%). The SDHB variants were the most frequently detected, followed by SDHA and SDHD variants. One case with SDHAF2 variant was bilateral CBT, and other two multiple PGL cases were not detected P/LP variants. The three cases with germline variants that could be tested did not have somatic P/LP variants of the same genes. Immunohistochemical analysis showed negative SDHB signals in CBT tissues in five cases with germline P/LP variants of SDHB, SDHD, or SDHA. In addition, SDHB signals in CBT tissues were negative in four of nine cases without germline P/LP variants of SDHs. These findings suggest the involvement of unidentified molecular mechanisms affecting SDHs. 相似文献
16.
Shuzo Oshita Yoshiki Fujiwara Hisashi Tamura Takefumi Sakabe Hiroshi Takeshita 《Journal canadien d'anesthésie》1994,41(6):534-541
To gain a better understanding of the direct actions of halothane on myocardial function in ischaemia, we studied the effects
of increasing extracellular potassium concentration and decreasing extracellular pH (acidosis), alone or in combination with
halothane, on the contractile force and resting tension in isolated atria. Guinea pig left atria were superfused with Tyrode’s
solution and stimulated at 1 Hz. Isometric contractile force and resting tension were measured using a force displacement
transducer. Perfusate potassium concentrations were increased from 5.4 mmol · L−1 to either 8.1 mmol · L−1 or 10.8 mmol · L−1 by adding KCl to the standard Tyrode’s solution, and its pH was decreased from 7.4 to either 7.0 or 6.5 by decreasing bicarbonate.
In standard Tyrode’s solution (potassium 5.4 mmol · L−1, pH 7.4), halothane 0.5–2% reduced contractile force in a dose-dependent manner (P < 0.05); the effective concentration of
halothane for 50% inhibition of contractile force (IC50) was 1.3%. Both increasing extracellular potassium and decreasing extracellular pH decreased the contractile force in a potassium-or
pH-dependent fashion. The negative inotropism of halothane (1%) was not altered by increasing potassium concentrations, whereas
1% halothane caused a greater decrease in contractile force at pH 6.5 than at pH 7.4. Halothane (1%) enhanced the acidosis
(pH 6.5)-induced increases in resting tension. Arrhythmias were produced in one of eight preparations during acidosis, while
four of eight preparations demonstrated arrhythmias during acidosis in the presence of halothane. These data suggest that
acidosis and halothane may have a synergistic interaction on the contractile force and resting tension of the atria. The increase
in resting tension observed during acidosis/ halothane conditions suggests than an increase in cytosolic calcium is associated
with these synergistic interactions between acidosis and halothane.
Pour mieux comprendre l’action direct de l’halothane sur la fonction myocardique pendant l’ischémie, nous avons étudié les
effets de l’augmentation du potassium extracellulaire et de la diminution du pH extracellulaire (acidose), seuls ou en association
avec l’halothane, sur la force contractile et la tension de repos d’oreillettes isolées. Des oreillettes gauches de cobaye
furent perfusées avec une solution de Tyrode et stimulées à 1 Hz. La force contractile isométrique et la tension de repos
ont été mesurées avec un transducteur de force de déplacement. Les concentrations de potassium perfusées ont été augmentées
de 5,4 mmol · L−1 à 8,1 mmol · L−1 ou à 10,8 mmol · L−1 par l’ajout de KCl à la solution standard de Tyrode, et son pH abaissé de 7,4 à 7,0 ou 6,5 par baisse des bicarbonates. Avec
la solution standard de Tyrode (potassium 5,4 mmol · L−1, pH 7,4), l’halothane (0.5–2%) diminue la force contractile proportionnellement à la dose (P < 0,05); la concentration efficace
d’halothane requise pour produire une inhibition de 50% de la force contractile (IC5O) a été de 1,3%. L’augmentation du potassium extracellulaire et la diminution du pH extracellulaire réduisent toutes les deux
la force contractile proportionnellement au potassium ou au pH. L’inotropisme négatif de l’halothane (1%) n’est pas modifié
par l’augmentation de la concentration de potassium alors que l’halothane produit une diminution plus importante de la force
contractile à un pH de 6,5 que de 7,4. L’halothane (1%) exagère l’augmentation de la tension de repos induite par l’acidose
(pH 6,5). Des arrythmies sont apparues sur une des huit préparations pendant l’acidose en présence d’halothane. Ces données
suggèrent que l’acidose et l’halothane pourraient avoir une activité synergique sur le force contractile et la tension de
repos des oreillettes. L’augmentation de la tension de repos observée pendant l’acidose combinée à l’halothane suggère l’association
d’une augmentation du calcium cytosolique avec des interactions synergiques entre l’acidose et l’halothane. 相似文献
17.
Matrix metalloproteinase-2 status in stromal fibroblasts, not in tumor cells, is a significant prognostic factor in non-small-cell lung cancer. 总被引:5,自引:0,他引:5
Shinya Ishikawa Kazumasa Takenaka Kazuhiro Yanagihara Ryo Miyahara Yozo Kawano Yosuke Otake Seiki Hasegawa Hiromi Wada Fumihiro Tanaka 《Clinical cancer research》2004,10(19):6579-6585
PURPOSE: The purpose is to assess clinical significance of matrix metalloproteinase (MMP)-2 and MMP-9 status, especially MMP-2 status, in stromal cells in non-small-cell lung cancer (NSCLC) because experimental studies have revealed that stromal MMP-2 plays important roles in progression of malignant tumors, but most clinical studies focused on tumoral MMP-2 expression, not stromal MMP-2 expression. EXPERIMENTAL DESIGN: We conducted a retrospective study on MMP-2 and MMP-9 expression as evaluated immunohistochemically in a total of 218 consecutive patients with completely resected pathological stage I-IIIA, NSCLC. RESULTS: Strong MMP-2 expression in tumor cells and stromal fibroblasts were documented in 54 (24.8%) and 132 (60.6%) patients, respectively. Strong MMP-2 expression in stromal fibroblasts was more frequently seen in squamous cell carcinoma (72.7%) than in adenocarcinoma (54.9%; P = 0.016). Tumors showing strong MMP-2 expression in stromal fibroblasts showed a significantly higher intratumoral microvessel density (IMVD) than weak stromal MMP-2 tumors (mean intratumoral microvessel density, 50.9 versus 32.4, P = 0.003). In addition, postoperative prognosis of strong stromal MMP-2 patients was significantly poorer than that of weak stromal MMP-2 patients (5-year survival rate, 77.5 versus 60.2%, P = 0.032), and the prognostic significance was enhanced in squamous cell carcinoma patients but disappeared in adenocarcinoma patients. Multivariate analyses confirmed that strong stromal MMP-2 expression was a significant factor to predict a poor prognosis in squamous cell carcinoma patients, not in adenocarcinoma patients. In contrast, MMP-2 or MMP-9 status in tumor cells was not a significant prognostic factor. CONCLUSIONS: MMP-2 status in stromal fibroblasts, not in tumor cells, was a significant prognostic factor associated with angiogenesis in NSCLC. 相似文献
18.
Nitric oxide does not play a major role in the regulation of systemic hemodynamic responses to acute normovolemic hemodilution 总被引:4,自引:0,他引:4
Hirose Y Kimura H Kitahata H Kawahito S Oshita S 《Acta anaesthesiologica Scandinavica》2000,44(1):96-100
Background: The mechanisms of cardiovascular changes following acute normovolemic hemodilution (ANH) have not been fully elucidated. We tested the hypothesis that inhibition of nitric oxide synthesis attenuates ANH-induced cardiovascular responses.
Methods: We observed the effects of Nω -nitro-L-arginine methyl ester (L-NAME) pretreatment on ANH-induced cardiovascular responses and compared these effects with those elicited by phenylephrine (PHE). Twenty dogs anesthetized with isoflurane were divided into two groups: one group was pretreated with L-NAME and the other with PHE. Both groups were normovolemically hemodiluted using 6% hydroxyethyl starch to reduce the hemoglobin concentration to approximately 50% of the pretreatment value.
Results: Pretreatment with either L-NAME or PHE caused a significant increase in mean aortic blood pressure (MAP) and systemic vascular resistance (SVR) with a significant decrease in cardiac output (CO) and stroke volume (SV). However, no remarkable differences in these variables were seen between groups. In both groups ANH produced increases in heart rate, CO, SV, and maximal left ventricular dP/dt with a significant decrease in SVR. No significant differences in these variables were apparent after ANH except that MAP was decreased in the PHE group but not in the L-NAME group.
Conclusion: Our results suggest that nitric oxide does not play a major role in mediation or modulation of the systemic vascular responses to ANH. 相似文献
Methods: We observed the effects of N
Results: Pretreatment with either L-NAME or PHE caused a significant increase in mean aortic blood pressure (MAP) and systemic vascular resistance (SVR) with a significant decrease in cardiac output (CO) and stroke volume (SV). However, no remarkable differences in these variables were seen between groups. In both groups ANH produced increases in heart rate, CO, SV, and maximal left ventricular dP/dt with a significant decrease in SVR. No significant differences in these variables were apparent after ANH except that MAP was decreased in the PHE group but not in the L-NAME group.
Conclusion: Our results suggest that nitric oxide does not play a major role in mediation or modulation of the systemic vascular responses to ANH. 相似文献
19.