全文获取类型
收费全文 | 114116篇 |
免费 | 30609篇 |
国内免费 | 1112篇 |
专业分类
耳鼻咽喉 | 2685篇 |
儿科学 | 2939篇 |
妇产科学 | 2540篇 |
基础医学 | 4617篇 |
口腔科学 | 6005篇 |
临床医学 | 27509篇 |
内科学 | 27698篇 |
皮肤病学 | 3454篇 |
神经病学 | 13937篇 |
特种医学 | 4193篇 |
外科学 | 20289篇 |
综合类 | 436篇 |
现状与发展 | 40篇 |
一般理论 | 25篇 |
预防医学 | 14862篇 |
眼科学 | 2375篇 |
药学 | 2267篇 |
1篇 | |
中国医学 | 21篇 |
肿瘤学 | 9944篇 |
出版年
2024年 | 747篇 |
2023年 | 5087篇 |
2022年 | 1212篇 |
2021年 | 2942篇 |
2020年 | 5458篇 |
2019年 | 2197篇 |
2018年 | 7086篇 |
2017年 | 7494篇 |
2016年 | 8084篇 |
2015年 | 8166篇 |
2014年 | 10708篇 |
2013年 | 12654篇 |
2012年 | 4495篇 |
2011年 | 4399篇 |
2010年 | 7278篇 |
2009年 | 9523篇 |
2008年 | 4388篇 |
2007年 | 3435篇 |
2006年 | 4641篇 |
2005年 | 3113篇 |
2004年 | 2475篇 |
2003年 | 2194篇 |
2002年 | 2104篇 |
2001年 | 2056篇 |
2000年 | 1358篇 |
1999年 | 1884篇 |
1998年 | 2302篇 |
1997年 | 2113篇 |
1996年 | 2165篇 |
1995年 | 1864篇 |
1994年 | 1244篇 |
1993年 | 1031篇 |
1992年 | 928篇 |
1991年 | 792篇 |
1990年 | 680篇 |
1989年 | 638篇 |
1988年 | 654篇 |
1987年 | 515篇 |
1986年 | 514篇 |
1985年 | 439篇 |
1984年 | 434篇 |
1983年 | 498篇 |
1982年 | 427篇 |
1981年 | 375篇 |
1980年 | 308篇 |
1978年 | 291篇 |
1977年 | 260篇 |
1976年 | 214篇 |
1974年 | 188篇 |
1972年 | 181篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
991.
Molecular genetic studies of early breast cancer evolution 总被引:9,自引:0,他引:9
Peter O'Connell PhD Vladimir Pekkel PhD Suzanne Fuqua PhD C. Kent Osborne MD D. Craig Allred MD 《Breast cancer research and treatment》1994,32(1):5-12
Summary In the past few years there has been an explosion in the number of patients diagnosed with hyperplastic breast disease andin situ breast cancer. Based on epidemiological data, these morphologically defined lesions may be categorized as those with little malignant potential (e.g. typical hyperplasia or proliferative disease without atypia [PDWA]), those with significant malignant potential which may already be initiated (e.g. atypical ductal hyperplasia [ADH]), and early transformed lesions which are malignant but not yet invasive (e.g. ductal carcinomain situ [DCIS]). They may represent sequential evolutionary stages in the ontogeny of invasive breast cancer, with each morphologically defined stage resulting from accumulating genetic changes culminating in a transformed clonal lineage capable of invasion and metastasis. Using loss-of-heterozygosity (LOH) analysis, we are studying the genetic changes associated with these lesions in archival tissue samples. 50% (6/12) of the proliferative lesions (PDWA and ADH) and 80% of the DCIS shared their LOH patterns with more advanced lesions from the same breast, strongly supporting a precursor/product relationship between these lesions and the cancers they accompany. 相似文献
992.
Verweij J.; Wanders J.; Nielsen A. L.; Pavlidis N.; Calabresi F.; Huinink W. ten Bokkel; Bruntsch U.; Piccart M.; Franklin H.; Kaye S. B.; On behalf of the EORTC Early Clinical Trials Group 《Annals of oncology》1994,5(4):375-376
PURPOSE:: To test the antitumor activity of Elsamitrucin in metastaticcancer of the breast, colon and rectum, non-small cell lungand ovary. PATIENTS AND METHODS:: Eligibility required histologically proven cancer. Patientswith colorectal or non-small cell lung cancer could not havereceived prior chemotherapy. Patients were entered if WHO PSwas 2 and organ functions were normal. Treatment consisted ofElsamitrucin 25 mg/m2/week given as a 510 min infusionfor at least 36 weekly doses. RESULTS:: One hundred and five patients entered the studies, 97 were eligible,94 are evaluable for toxicity and 75 for response. Toxicitymainly consisted of mild nausea/vomiting, and less frequentlyreversible hepatotoxicity and malaise. No objective responseswere seen. CONCLUSION:: Elsamitrucin at this dose and schedule is not an active drugin metastatic breast cancer, colorectal cancer, non-small celllung cancer or ovarian cancer. Elsamitrucin, phase II, breast, colorectum, nonsmall cell lung, ovary 相似文献
993.
Dr. D. M. McKay PhD M. Benjamin BSc M. Baca-Estrada PhD R. D'Inca MD K. Croitoru MD M. H. Perdue PhD 《Digestive diseases and sciences》1995,40(2):331-337
Athymic (nude) rats have been used to assess the role of thymus-dependent T cells in the control of the intestinal response following infection with the enteric parasite,Nippostrongylus brasiliensis. Tissues from infected rats were excised on days 4, 7, 10, and 21 postinfection (p-i) for physiological and morphological studies; uninfected (day 0) rats served as controls. In response to the worm burden, jejunal tissues displayed a secretory response, indicated by an elevated baseline short-circuit current (I
sc
) on days 7 and 10 p-i, and were more responsive to histamine than control tissues. Despite this enhanced secretory response, 35% of the worm burden was still present on day 21 p-i (compared with expulsion of >95% by day 14 p-i in normal rats). Mast cell activation and hyperplasia, increased goblet cell (implying increased mucus synthesis) and intraepithelial leukocyte numbers, and abnormalities inI
sc
responses after electrical stimulation of enteric nerves were identified following infection. These events in nude rats were attenuated or delayed in onset as compared with conventional immunocompetent rats. Our results support the postulate that thymus-dependent T cells regulate the timing and/or nature of the mucosal response to enteric parasitic infections. However, ion secretion was not altered in the absence of T cells and, therefore, is more likely to be a consequence of mast cell activation.This work was conducted with financial support from The Canadian Medical Research Council and the National Institutes of Health (NS 29536). 相似文献
994.
Jack C. Kim Mi-Hyang Kim Seon-Hee Kim Soon-Kyu Choi 《Archives of pharmacal research》1995,18(6):449-453
The search for platinum (II)-based compounds with improved therapeutic properties was prompted to design and synthesize a new family of water-soluble, third generation cis-diamminedichloroplatinum (II) complexes linked to uracil and uridine. Six heretofore undescribed uracil and uridine-platinum (II) complexes are; [N-(2-aminoethyl)uracil-5-carboxamide]dichloroplatinum (II) (3a), [N-(2-aminoethyl)uracil-6-carboxamide]dichloroplatinum (II) (3b), [5-(2-aminoethyl)carbamoyl-2′,3′,5′,-tri-O-acetyluridine] dichloroplatinum (II) (6b), [5-(2-aminoethyl) carbamoylu-carbamoyl-2′,3′,5′,-tri-O-acetyluridine] dichloroplatinum (II) (6b), [5-(2-aminoethyl)carbamoyluridine]dichloroplatinum (II) (7a), [6-(2-aminoethyl)carbamoyluridine]dichloroplatinum (II) (7b). These analogues were prepared from the key starting materials, 5-carboxyuracil (1a) and 6-carboxyuracil (1b) which were reacted with ethylenediamine to afford the respective N-(2-aminoethyl)uracil-5-carboxamide (2a) and N-(2-aminoethyl)uracil-6-carboxamide (2b). The cisplatin complexes3a and3b were obtained through the reaction of the respective2a and2b with potassium tetrachloroplatinate (II). The heterocyclic nucleic acid bases1a and1b were efficiently introduced on the β-D-ribose ring via a Vorbruggen-type nucleoside coupling procedure with hexamethyldisilazane, trimethylchlorosilane and stannicchloride under anhydrous acetonitrile to yield the stereospecific β-anomeric 5-carboxy-2′,3′,5′-tri-0-acetyluridine (4a) and 6-carboxy-2′,3′,5′-tri-0-acetyluridine (4b), respectively. The nucleosides4a and4b were coupled with ethylenediamine to provide the respective 5-(2-aminoethyl)carbamoyl-2′,3′,5′-tri-0-acetyluridine (5a) and 6-(2-aminoethyl)carbamoyl-2′,3′,5′-tri-0-acetyluridine (5b). The diamino-uridines5a and5b were reacted with potassium tetrachloroplatinate (II) to give the novel nucleoside complexes,6a and6b, respectively which were deacetylated into the free nucleosides,7a and7b by the treatment with CH3ONa. The antitumor activities were evaluated against three cell lines (K-562, FM-3A and P-388). 相似文献
995.
Jesús Ruiz-Cabello Kirsten Berghmans Ofer Kaplan Marc E. Lippman Robert Clarke Jack S. Cohen 《Breast cancer research and treatment》1995,33(3):209-217
Many breast tumors appear to progress from estrogen-dependent growth to a more malignant phenotype characterized by estrogen-independent growth, antiestrogen resistance, and a high metastatic potential. Utilizing31P NMR spectroscopy on human breast cancer cells growingin vitro, we have investigated the effects of 17-estradiol and tamoxifen on the metabolic/bioenergetic spectra of a series of human breast cancer cells that vary in their estrogen and antiestrogen responsiveness. A comparison of baseline spectra associates higher levels of phosphodiesters and UDP-glucosides (e.g. UDP-glucose, UDP-N-acetylglucosamine), and lower phosphocholine/glycerylphosphocholine and phosphocholine/phosphoethanolamine ratios, with the acquisition of estrogen-independent growth in estrogen receptor expressing cells. No metabolic changes are clearly associated with the metastatic phenotype. Whilst estrogen treatment produces no consistently significant spectral changes in any of the cell lines, the estrogen-independent and estrogen-responsive MCF7/MIII cell line responds to tamoxifen treatment by significantly increasing all spectral resonances 30%-40% above baseline values. This may reflect a tamoxifen-induced change to a more differentiated or apoptotic phenotype, or an attempt by the cells to reverse the inhibitory effects of the drug. The ability to detect metabolic changes in response to tamoxifen by NMR spectroscopy may provide a novel means to identify those tumors that are responsive to antiestrogen therapy.Abbreviations CCS-IMEM
steroid-deprived Improved Minimal Essential Medium
- E2
17-estradiol
- ER
estrogen receptor
- Pi
inorganic phosphate
- GPE
glyceryl-phosphoethanolamine
- GPC
glyceryl-phosphocholine
- PC
phosphocholine
- PE
phosphoethanolamine
- PDE
phosphodiesters
- PME
phosphomonoesters
- TAM
tamoxifen (trans-1-(4--dimethylaminoethoxyphenyl)-1,2-diphenylbut-1-ene)
- UDPG
uridine diphosphoglycoside 相似文献
996.
Nogah Haramati M.D. Nurith Hiller M.D. Jack Dowdle M.D. Mark Jacobson M.D. Charles N. Barax M.D. Ross I. Lieberfarb M.D. Benisse Lester M.D. Roy G. Kulick M.D. 《Skeletal radiology》1995,24(7):515-518
Objective. To assess the utility of MR in detecting surgically induced Stener lesions (displaced thumb ulnar collateral ligaments) in cadaveric models.
Design. Six cadaver thumbs had ulnar collateral ligament (UCL) tears created surgically. MR examinations (2D STIR and 3D GRASS) were performed identically on all specimens both before displacement (non-Stener) and after displacement (Stener lesion) of the UCL. The MR images were then randomly numbered. Each image was evaluated separately in blinded fashion by four musculoskeletal radiologists for the presence or absence of a Stener lesion. Each radiologist reinterpreted the images after an interval of several days. The interpretation was based on previously published criteria for Stener lesion diagnosis by MR.
Results. The sensitivity of GRASS ranged from 0.17 to 0.67 with the most experienced reader scoring the lowest. The specificity of GRASS ranged from 0.33 to 1.0 (most experienced reader 0.67, 0.83). STIR had a sensitivity of 0.00–0.17 and a specificity of 0.53–0.83. The values for inter- and intraobserver agreement were measured. The intraobserver for GRASS was 0.27–0.75 (most experienced reader 0.75).
Conclusions. 2D imaging is probably inadequate for the evaluation of Stener lesions. The most likely reason is that the STIR slice thickness of 3 mm limits resolution of small UCLs. The poor sensitivity and specificity of GRASS as well as poor interobserver agreement suggest that MR may not be sufficiently accurate for Stener lesion evaluation. 相似文献
997.
Background: upper body, or abdominal, distribution of body fat is associated with a number of metabolic and hormonal aberrations
that could influence resting energy expenditure REE. The purpose of our study was to examine the effects of fat distribution
on REE of 96 morbidly obese premenopausal females. Methods: the study population consisted of three groups of study subjects,
32 with lower body fat distribution (LBD) and waist-to-hip circumference ratios WHR < 0.80, 20 with intermediate (INT) fat
distribution and WHR between 0.80 and 0.85 and 34 females with upper body distribution of fat (UBD) and WHR > 0.85. Indices
measured included: (1) REE; (2) maximal oxygen consumption during an exercise tolerance test (VO2max); (3) basal respiratory quotient (RQ); (4) fasting blood glucose; and (5) serum cholesterol and triglycerides. Results: we
found that morbidly obese women who store fat abdominally (WHR > 0.80) have significantly (p < 0.01) higher REE (kcal per h per BSA) than those with lower body obesity. Levels of triglyceride and glucose of the UBD
group were also higher than those of the LBD subjects, i.e. 35% and 23%, respectively. VO2max and RQ were similar between the study groups, suggesting that the elevated REE of the patients with abdominal adiposity were
likely not the result of their greater muscle mass or differences in substrate utilization. Conclusion: fat distribution affects
REE in morbidly obese premenopausal females, and further research is needed to identify the various entities regulating REE
in the morbidly obese. 相似文献
998.
999.
Background: Gastric banding is one of the simplest surgical procedures for the treatment of morbid obesity. We performed more
than 150 ‘laparotomy’ (open) gastric bandings and more than 50 ‘laparoscopic’ bandings in the last 10 years. Methods: In most
procedures we used non-adjustable bands, but since the beginning of 1995 we have used adjustable silicone banding. Results:
The 5- and 10-year follow-up weight loss results are encouraging. The average long-term weight loss was 35.5 kg. Since 1993,
we performed all the procedures laparoscopically, and the postoperative complications decreased from 18.5% in the ‘laparotomy’
group to 9.5% in the ‘laparoscopic’ group, with the majority being esophagitis and outlet area irritation. Conclusion: Gastric
banding itself and especially the minimally invasive laparoscopic approach is an easy technical procedure. The long-term weight
loss results and the reoperation rate are acceptable for bariatric surgery criteria. 相似文献
1000.
Background: this study was designed to characterize some of the biochemical and molecular genetic changes during reversion
of human fat cells. Methods: mature adipocytes were isolated from greater omental fat tissue of eight lean and 14 massively
obese persons by established methodology. Results: at day 7 of adherence to Leighton tubes, there was appreciable depletion
of triacylglycerol, as well as assumption of an elongated contour. Relatedly, there was an increase in the expression of β-actin
mRNA and a significant decrease in the specific activity of cytosolic glycerophosphate dehydrogenase. The decrement in the
specific activity of glycerophosphate dehydrogenase, after 7 days in culture, was significant at p < 0.001. Basic fibroblast growth factor at 10 ngml-1 accelerated significantly (p < 0.03) the decrease in the specific activity of glycerophosphate dehydrogenase in adipose cells from lean subjects. In contrast,
basic fibroblast growth factor had no significant influence on cells from massively obese persons. Conclusion: such resistance
may contribute to the intractability of massive obesity. 相似文献