全文获取类型
收费全文 | 11927篇 |
免费 | 721篇 |
国内免费 | 85篇 |
专业分类
耳鼻咽喉 | 179篇 |
儿科学 | 416篇 |
妇产科学 | 260篇 |
基础医学 | 1510篇 |
口腔科学 | 256篇 |
临床医学 | 960篇 |
内科学 | 2804篇 |
皮肤病学 | 456篇 |
神经病学 | 820篇 |
特种医学 | 505篇 |
外科学 | 1627篇 |
综合类 | 273篇 |
一般理论 | 2篇 |
预防医学 | 990篇 |
眼科学 | 165篇 |
药学 | 667篇 |
中国医学 | 125篇 |
肿瘤学 | 718篇 |
出版年
2023年 | 70篇 |
2022年 | 163篇 |
2021年 | 384篇 |
2020年 | 147篇 |
2019年 | 308篇 |
2018年 | 404篇 |
2017年 | 232篇 |
2016年 | 210篇 |
2015年 | 281篇 |
2014年 | 452篇 |
2013年 | 549篇 |
2012年 | 598篇 |
2011年 | 676篇 |
2010年 | 430篇 |
2009年 | 446篇 |
2008年 | 590篇 |
2007年 | 579篇 |
2006年 | 543篇 |
2005年 | 556篇 |
2004年 | 555篇 |
2003年 | 572篇 |
2002年 | 531篇 |
2001年 | 404篇 |
2000年 | 431篇 |
1999年 | 338篇 |
1998年 | 113篇 |
1997年 | 95篇 |
1996年 | 108篇 |
1995年 | 74篇 |
1994年 | 64篇 |
1993年 | 66篇 |
1992年 | 190篇 |
1991年 | 161篇 |
1990年 | 153篇 |
1989年 | 144篇 |
1988年 | 144篇 |
1987年 | 122篇 |
1986年 | 106篇 |
1985年 | 101篇 |
1984年 | 75篇 |
1983年 | 49篇 |
1982年 | 33篇 |
1981年 | 32篇 |
1979年 | 54篇 |
1978年 | 31篇 |
1977年 | 32篇 |
1976年 | 33篇 |
1975年 | 44篇 |
1974年 | 43篇 |
1972年 | 28篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
71.
J. Pressmar H. Brinkmeier M. J. Seewald T. Naumann R. Rüdel 《Pflügers Archiv : European journal of physiology》1994,426(6):499-505
The free intracellular calcium concentration, [Ca2+]i, was studied in single myotubes using the fluorescent Ca2+ indicator fura-2. Myotubes cultured from satellite cells of small muscle specimens from Duchenne muscular dystrophy (DMD) patients were compared with human control myotubes and with myotubes cultured from MDX and control mouse muscle satellite cells. The resting [Ca2+]i levels in DMD and control myotubes were not significantly different, i. e. 104 ±26 nM (mean ± SD, n=190 cells from eight DMD patients) compared with 97±25 nM (175/seven controls) and were not significantly lower than the corresponding murine values (154±33 nM, n=135 MDX myotubes; 159±34 nM, n=135 controls). All myotubes reacted to 10 M acetylcholine or 40 mM KCl with fast transient increases of [Ca2+]i. After application of a hyposmotic (130 mOsm) solution, [Ca2+]i was increased 1.5- to 3-fold within 2–3 min, the DMD myotubes tending to stronger reactions (significantly higher [Ca2+]i in 2 out of 6 cases). The response was usually transient, [Ca2+]i decreasing to the initial level within 10 min. Gadolinium (50 M) reduced the response by 50%–70%, indicating that the osmotic shock increased Ca2+ influx. During exposure to high (15 mM) [Ca2+]e, [Ca2+]i of DMD and control cells was 1.5- to 2-fold higher. Adult muscle fibres from MDX mice and controls showed identical Ca2+ resting levels (n=45 fibres from three mice in each case), but did not respond to decreased external osmolarity with a change in [Ca2+]i. The results indicate that lack of dystrophin in muscle fibres does not necessarily lead to increased [Ca2+]i. It is suggested that increased [Ca2+]i is probably a secondary consequence of fibre damage. 相似文献
72.
Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability 总被引:1,自引:15,他引:1
La Spada AR; Peterson KR; Meadows SA; McClain ME; Jeng G; Chmelar RS; Haugen HA; Chen K; Singer MJ; Moore D; Trask BJ; Fischbeck KH; Clegg CH; McKnight GS 《Human molecular genetics》1998,7(6):959-967
X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG
repeat expansion in the first exon of the androgen receptor (AR) gene.
Disease-associated alleles (37-66 CAGs) change in length when transmitted
from parents to offspring, with a significantly greater tendency to shift
size when inherited paternally. As transgenic mice carrying human AR cDNAs
with 45 and 66 CAG repeats do not display repeat instability, we attempted
to model trinucleotide repeat instability by generating transgenic mice
with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions
in their genomic context. Studies of independent lines of AR YAC transgenic
mice with CAG 45 alleles reveal intergenerational instability at an overall
rate of approximately 10%. We also find that the 45 CAG repeat tracts are
significantly more unstable with maternal transmission and as the
transmitting mother ages. Of all the CAG/CTG repeat transgenic mice
produced to date the AR YAC CAG 45 mice are unstable with the smallest
trinucleotide repeat mutations, suggesting that the length threshold for
repeat instability in the mouse may be lowered by including the appropriate
flanking human DNA sequences. By sequence-tagged site content analysis and
long range mapping we determined that one unstable transgenic line has
integrated an approximately 70 kb segment of the AR locus due to
fragmentation of the AR YAC. Identification of the cis - acting elements
that permit CAG tract instability and the trans -acting factors that
modulate repeat instability in the AR YAC CAG 45 mice may provide insights
into the molecular basis of trinucleotide repeat instability in humans.
相似文献
73.
Arcos D del Real RP Vallet-Regí M 《Journal of biomedical materials research. Part A》2003,65(1):71-78
Three biphasic materials have been synthesized from a magnetic glass-ceramic (Si-Ca-Fe) and a bioactive sol-gel glass (Si-P-Ca). The ratios of glass-ceramic:sol-gel glass used in this work were 1:1, 2:1, and 5:1. These materials show bioactive and magnetic properties and can be used as thermoseeds for hyperthermia treatment of bone tumors. The sol-gel glass content affects the textural properties of the glass-ceramic, giving rise to porosity, which plays a fundamental role in the formation of an apatite-like layer on the surface. On the other hand, as the sol-gel glass content increases, the magnetic properties change due to the diffusion of Fe ions to the glassy phases of the biphasic materials. The biphasic nature of these materials allows the changing of both properties, depending on the requirements of the patient. 相似文献
74.
75.
PTEN mutations in endometrial carcinomas: a molecular and clinicopathologic analysis of 38 cases 总被引:23,自引:0,他引:23
PTEN mutations have been reported to be frequent in endometrioid carinomas of the endometrium (EEC). Some correlation has been found between PTEN mutations and the presence of microsatellite instability (MI) in EEC, but no convincing cause-effect relationship for such association has been offered. DNA of 38 patients with endometrial carcinoma (EC) was extracted from blood and from fresh-frozen and paraffin-embedded tumor tissue. PTEN mutations were detected by single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. Results were correlated with MI status and clinicopathologic data. PTEN mutations were detected in 17 tumors (44.7%), and they were more frequent in endometrioid (EEC) (17 of 33, 51.5%) than in nonendometrioid carcinomas (NEEC) (0 of 5, 0%). PTEN mutational spectrum differed between MI+ and MItumors. PTEN mutations were detected in 9 of 15 MI+ tumors (60%), but in only 8 of 23 MI- neoplasms (34.8%). In EC with MI, PTEN mutations were detected in short coding mononucleotide repeats (A)s and (A)6 in 4 of 9 carcinomas (44.4%). These results confirm that PTEN is an important target gene in endometrial carcinogenesis. The occurrence of PTEN mutations in short coding mononucleotide repeats in MI-positive tumors suggests that these mutations may be secondary to deficiencies in mismatch repair and gives some explanation for the frequent presence of PTEN mutations in these tumors. 相似文献
76.
Relating cistrons and functions in bacteriophage PM2 总被引:1,自引:0,他引:1
An approach to correlate functions with cistrons in bacteriophage PM2 is presented. Two of the temperature-sensitive mutants obtained differed from the wild type in heat sensitivity and four differed in host range. Comparison of the electrophoretic patterns of DNA from cells infected at the restrictive temperature with those obtained in wildtype infection revealed that viral DNA bands were absent with three additional mutants. Complementation analysis assigned the four host range mutants to cistron I and the three mutants defective in DNA synthesis to cistron IV. Recombination frequencies were used to locate cistrons III and IV on the partial genetic map of PM2. 相似文献
77.
Franz Zite-Ferenczy Reinhardt Rüdel 《Pflügers Archiv : European journal of physiology》1978,374(1):97-100
A simple method is devised to record rapid sarcomere length changes of muscle fibres using a lateral effect diode. In the standard position the diffractometer records length changes between 1.65 and 3.8 m, the output being linear 1 V/m with a frequency response of –3 dB at 1.2 kHz. The absolute error is<0.05 m between 1.65 and 2.80 m and <0.1 m between 2.81 and 3.30 m. The resolution of length changes is<0.005 m over the whole range. By varying the detector position the length range can be extended to either side, and spatial resolution can be improved at the expense of length range. 相似文献
78.
D Acu?a Castroviejo C M del Aguila B Fernández M D Gomar J L Castillo 《Neuroscience letters》1991,127(2):227-230
The effect of the pineal gland on the ouabain high-affinity binding sites (Kd = 3.1 +/- 0.4 nM, Bmax = 246.4 +/- 18.4 fmol/mg protein) in rat cerebral cortex was studied. Pinealectomy increased Bmax (940.7 +/- 42.8 fmol/mg protein) and Kd (7.6 +/- 1.5 nM) while melatonin injection (100 micrograms/kg b.wt.) counteracted these effects, restoring kinetic parameters (Kd = 1.9 +/- 0.05 nM; Bmax = 262.2 +/- 29.6 fmol/mg prot) to control values. Melatonin activity on ouabain binding in vitro did not depend upon a direct effect on the binding sites themselves. However, in competition experiments, melatonin increased binding affinity of ouabain as shown by the decreased IC50 values. 相似文献
79.
Prevalence and risk factors of tinea unguium and tinea pedis in the general population in Spain 下载免费PDF全文
Perea S Ramos MJ Garau M Gonzalez A Noriega AR del Palacio A 《Journal of clinical microbiology》2000,38(9):3226-3230
This study prospectively evaluated the prevalence and risk factors of tinea unguium and tinea pedis in the general adult population in Madrid, Spain. One thousand subjects were clinically examined, and samples of nails and scales from the interdigital spaces of the feet were taken from those patients presenting with signs or symptoms of onychomycosis and/or tinea pedis, respectively. In addition, a sample from the fourth interdigital space of both feet was collected from all individuals with a piece of sterilized wool carpet. Tinea unguium was defined as a positive direct examination with potassium hydroxide and culture of the etiological agent from subjects with clinically abnormal nails. Patients with positive dermatophyte cultures of foot specimens were considered to have tinea pedis. The prevalence of tinea unguium was 2.8% (4.0% for men and 1.7% for women), and the prevalence of tinea pedis was 2.9% (4.2% for men and 1.7% for women). The etiological agents of tinea unguium were identified as Trichopyton rubrum (82.1%), followed by Trichopyton mentagrophytes var. interdigitale (14.3%) and Trichopyton tonsurans (3.5%). Trichophyton rubrum (44.8%) and Trichophyton mentagrophytes (44.8%), followed by Epidermophyton floccosum (7%) and T. tonsurans (3.4%), were the organisms isolated from patients with tinea pedis. The percentage of subjects who suffered simultaneously from both diseases was 1.1% (1.7% for men and 0.6% for women). In a multivariate logistic regression analysis, age (relative risk [RR], 1.03) and gender (RR, 2.50) were independent risk factors for tinea unguium, while only gender (RR, 2.65) was predictive for the occurrence of tinea pedis. In both analyses, the presence of one of the two conditions was associated with a higher risk for the appearance of the other disease (RR, >25). 相似文献
80.
Chronic cyclosporin A nephrotoxicity, P-glycoprotein overexpression, and relationships with intrarenal angiotensin II deposits. 下载免费PDF全文
R. G. del Moral M. Andujar C. Ramírez M. Gmez-Morales M. Masseroli M. Aguilar A. Olmo F. Arrebola M. Guilln M. J. García-Chicano F. F. Nogales F. O'Valle 《The American journal of pathology》1997,151(6):1705-1714
P-glycoprotein (P-gp) expels hydrophobic substances from the cell, including chemotherapeutic agents and immunosuppressants such as cyclosporin A (CsA) and FK506. Exposure of cultured renal tubular cells to CsA induces P-gp overexpression in cell membranes. Angiotensin II has recently been implicated as the principal factor responsible for progression of interstitial fibrosis induced by CsA. To investigate the in vivo relationships between histological lesions, P-gp overexpression, and intrarenal angiotensin II deposits, we developed a model of chronic CsA toxicity in Sprague-Dawley rats treated with 25 mg/kg/day CsA for 28 and 56 days and fed either a standard maintenance diet or a low-salt diet. Immunohistochemical methods were used to study the expression of P-gp in renal tubular cells and the appearance of intrarenal angiotensin II deposits. Rats treated with CsA developed chronic nephrotoxicity lesions that were more evident in the group fed the low-salt diet. Treatment with CsA induced overexpression of P-gp in tubular cells of the kidney that increased with time. We found that immunohistochemical expression of P-gp was slightly more severe in rats fed a low-salt diet. Intrarenal deposits of angiotensin II were more evident in rats treated with CsA; these deposits also increased with time. This finding was also more relevant in rats given the low-salt diet. The up-regulation of P-gp was inversely related to the incidence of hyaline arteriopathy (r = -0.65; P < 0.05), periglomerular (r = -0.58; P < 0.05) and peritubular fibrosis (r = -0.63; P < 0.05), and intrarenal angiotensin H deposits in animals with severe signs of nephrotoxicity (r = -0.65; P < 0.05). These results support the hypothesis that the role of P-gp as a detoxicant in renal cells may be related to mechanisms that control the cytoplasmic removal of both toxic metabolites from CsA and those originating from the catabolism of signal transduction proteins (methylcysteine esters), which are produced as a result of ras activation in presence of angiotensin II. 相似文献