全文获取类型
收费全文 | 17062篇 |
免费 | 1441篇 |
国内免费 | 940篇 |
专业分类
耳鼻咽喉 | 153篇 |
儿科学 | 205篇 |
妇产科学 | 335篇 |
基础医学 | 2086篇 |
口腔科学 | 348篇 |
临床医学 | 2264篇 |
内科学 | 2689篇 |
皮肤病学 | 242篇 |
神经病学 | 874篇 |
特种医学 | 561篇 |
外国民族医学 | 7篇 |
外科学 | 1831篇 |
综合类 | 2440篇 |
现状与发展 | 1篇 |
一般理论 | 11篇 |
预防医学 | 958篇 |
眼科学 | 421篇 |
药学 | 1755篇 |
8篇 | |
中国医学 | 695篇 |
肿瘤学 | 1559篇 |
出版年
2024年 | 62篇 |
2023年 | 274篇 |
2022年 | 629篇 |
2021年 | 741篇 |
2020年 | 553篇 |
2019年 | 541篇 |
2018年 | 592篇 |
2017年 | 485篇 |
2016年 | 446篇 |
2015年 | 724篇 |
2014年 | 911篇 |
2013年 | 915篇 |
2012年 | 1308篇 |
2011年 | 1424篇 |
2010年 | 900篇 |
2009年 | 709篇 |
2008年 | 888篇 |
2007年 | 921篇 |
2006年 | 860篇 |
2005年 | 829篇 |
2004年 | 583篇 |
2003年 | 554篇 |
2002年 | 403篇 |
2001年 | 374篇 |
2000年 | 378篇 |
1999年 | 438篇 |
1998年 | 274篇 |
1997年 | 280篇 |
1996年 | 188篇 |
1995年 | 173篇 |
1994年 | 145篇 |
1993年 | 105篇 |
1992年 | 112篇 |
1991年 | 86篇 |
1990年 | 77篇 |
1989年 | 77篇 |
1988年 | 94篇 |
1987年 | 85篇 |
1986年 | 57篇 |
1985年 | 51篇 |
1984年 | 25篇 |
1983年 | 23篇 |
1982年 | 22篇 |
1981年 | 14篇 |
1980年 | 15篇 |
1979年 | 28篇 |
1978年 | 11篇 |
1977年 | 8篇 |
1975年 | 10篇 |
1974年 | 8篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
992.
993.
994.
Age-Related Bone Mineral Density, Accumulated Bone Loss Rate and Prevalence of Osteoporosis at Multiple Skeletal Sites in Chinese Women 总被引:18,自引:0,他引:18
Er-Yuan Liao Xian-Ping Wu Xiao-Ge Deng Gan Huang Xu-Ping Zhu Zhao-Feng Long Wen-Bo Wang Wei-Li Tang Hong Zhang 《Osteoporosis international》2002,13(8):669-676
We investigated the age-related bone mineral density (BMD), accumulated bone loss rate (ABLR) and the prevalence of osteoporosis
at different skeletal sites in Chinese women. BMD was measured at the anteroposterior (AP) spine, supine lateral spine (areal
BMD at the midarea [mLat] and the whole region [Lat], volumetric BMD at the middle region [MVD] and total region [TVD]), hip
(femoral neck [FN], trochanter [Troc] and Ward’s triangle [Ward’s]) and forearm (radius + ulna ultradistal [RUUD], 1/3 region
[RU1/3] and total region [RUT]) using a dual-energy X-ray absorptiometry (DXA) fan-beam bone densitometer (Hologic QDR 4500A)
in 2702 females aged from 5 to 96 years old. Data were analyzed by eight different regression models. We found that the cubic
regression model was the best for describing age-related changes in BMD. The coefficients of determination (R
2) of the fitting curve were 0.398 to 0.612 (p= 0.000). The data were then analyzed by 5-year age groups. This showed that the earliest peak BMD was at the age of 20–24
years at Troc and Ward’s, and the latest at the age of 40–44 years at RU1/3 and RUT of the distal forearm. Compared with BMD,
the ABLRs were highest at Ward’s (−66.2%) and the lowest at RU1/3 of the distal forearm (−31.3%) in subjects over 80 years
old. The prevalence of osteoporosis at at least one site in these women was 0.5 ± 0.4% in those 30–39, 4.6 ± 4.4% in those
40–49, 23.9 ± 13.3% in those 50–59, 56.3 ± 20.3% in those 60–69, 71.8 ± 16.7% in those 70–79 and 83.2 ± 12.1% those over 80
years of age, respectively. The prevalence of osteoporosis in these women was 8.6–11.1% at the age of 40–49 and 36.5–40.6%
at the age of 50–59 at the lateral spine regions (mLat, Lat, MVD and TVD), and 0.5–3.7% at the age of 40–49 and and 3.9–21.7%
at the age of 50–59 years at the other skeletal sites (AP, FN, Troc, Ward’s, RUUD, RU1/3 and RUT). Significant differences
were found in the prevalence of osteoporosis between the lateral spine regions and other skeletal sites (p<0.001) at the age of 40–59 years. In summary, we demonstrated significant age-related differences in peak BMD, ABLR and osteoporosis
prevalence among various skeletal sites. Our data suggest that the supine lateral spine is the most sensitive site for the
diagnosis of osteoporosis, especially in the early menopausal period, although the prevalence of osteoporosis varied with
age and with different sites measured.
Received: 20 November 2001 / Accepted: 13 February 2002 相似文献
995.
Structure-activity relationships for inhibition of human 5alpha-reductases by polyphenols 总被引:11,自引:0,他引:11
The enzyme steroid 5 alpha-reductase (EC 1.3.99.5) catalyzes the NADPH-dependent reduction of the double bond of a variety of 3-oxo-Delta(4) steroids including the conversion of testosterone to 5 alpha-dihydrotestosterone. In humans, 5 alpha-reductase activity is critical for certain aspects of male sexual differentiation, and may be involved in the development of benign prostatic hyperplasia, alopecia, hirsutism, and prostate cancer. Certain natural products contain components that are inhibitors of 5 alpha-reductase, such as the green tea catechin (-)-epigallocatechin gallate (EGCG). EGCG shows potent inhibition in cell-free but not in whole-cell assays of 5 alpha-reductase. Replacement of the gallate ester in EGCG with long-chain fatty acids produced potent 5 alpha-reductase inhibitors that were active in both cell-free and whole-cell assay systems. Other flavonoids that were potent inhibitors of the type 1 5alpha-reductase include myricetin, quercitin, baicalein, and fisetin. Biochanin A, daidzein, genistein, and kaempferol were much better inhibitors of the type 2 than the type 1 isozyme. Several other natural and synthetic polyphenolic compounds were more effective inhibitors of the type 1 than the type 2 isozyme, including alizarin, anthrarobin, gossypol, nordihydroguaiaretic acid, caffeic acid phenethyl ester, and octyl and dodecyl gallates. The presence of a catechol group was characteristic of almost all inhibitors that showed selectivity for the type 1 isozyme of 5 alpha-reductase. Since some of these compounds are consumed as part of the normal diet or in supplements, they have the potential to inhibit 5 alpha-reductase activity, which may be useful for the prevention or treatment of androgen-dependent disorders. However, these compounds also may adversely affect male sexual differentiation. 相似文献
996.
Effects of Sucrose and Trehalose on the Preservation of the Native Structure of Spray-Dried Lysozyme 总被引:2,自引:0,他引:2
Purpose. To investigate the effects of sucrose, trehalose, sucrose/dextran mixtures, and sucrose/trehalose mixtures on the preservation of the native structure of spray-dried lysozyme in the solid state.
Methods. The intensity of the -helical band and the melting enthalpies (Hm ) of spray-dried lysozyme in the dried form and in aqueous solution were obtained using second derivative FTIR and differential scanning calorimetry (DSC) respectively.
Results. The intensity of the -helical band and the H m of spray-dried lysozyme obtained were linearly correlated and both suggest that the stabilization of lysozyme in the dried form was excipient concentration-dependent with a close to maximum stabilization being conferred by sucrose or trehalose at a mass ratio 1–2 (sugar:enzyme). Sucrose appeared to be more effective than trehalose on a weight by weight basis whilst stabilizing effects of dextran/sucrose or trehalose/sucrose mixtures were found to be additive.
Conclusion. Dehydration during spray drying was considered the main stress to the denaturation of lysozyme. A major effect of the sugars in protecting lysozyme against dehydration was attributable to hydrogen bonding between the sugar and protein molecules, which lead to an increase in the change in the negative value of the free energy between native and denatured states. 相似文献
997.
998.
Nuclear factor-kappaB (NF-kappaB) has been implicated in the development of drug resistance in cancer cells. We systematically examined the baseline levels of NF-kappaB activity of representative carcinoma cell lines, and the change of NF-kappaB activity in response to a challenge with four major anticancer drugs (doxorubicin, 5-fluorouracil, cisplatin, and paclitaxel). We found that the basal level of NF-kappaB activity was heterogeneous and roughly correlated with drug resistance. When challenged with various drugs, all the cell lines examined responded with a transient activation of NF-kappaB which then declined to basal level despite variation in the concentration of the agent and the timing of the treatment. In contrast to tumor necrosis factor-alpha (TNF-alpha), which activates NF-kappaB in minutes, NF-kappaB activation induced by anticancer drugs usually occurred more than 1hr after stimulation. A gradual increase of total NF-kappaB and its nuclear translocation, and cytoplasmic translocation of nuclear IkappaBalpha and its degradation were involved in this process. In particular, when cells were pretreated with common biologic modulators such as tamoxifen, dexamethasone, and curcumin, the doxorubicin-induced NF-kappaB activation was attenuated significantly. This inhibition may play a role in sensitizing cancer cells to chemotherapeutic drugs. This study has demonstrated that activation of NF-kappaB is a general cellular response to anticancer drugs, and the mechanism of activation appears to be distinct from that induced by TNF-alpha. These observations may have implications for improving the efficacy of systemic chemotherapy for cancer patients. 相似文献
999.
Singh J Van Vlijmen H Liao Y Lee WC Cornebise M Harris M Shu IH Gill A Cuervo JH Abraham WM Adams SP 《Journal of medicinal chemistry》2002,45(14):2988-2993
The antigen alpha4beta1 (very late antigen-4, VLA-4) plays an important role in the migration of white blood cells to sites of inflammation. It has been implicated in the pathology of a variety of diseases including asthma, multiple sclerosis, and rheumatoid arthritis. We describe a series of potent inhibitors of alpha4beta1 that were discovered using computational screening for replacements of the peptide region of an existing tetrapeptide-based alpha4beta1 inhibitor (1; 4-[N'-(2-methylphenyl)ureido]phenylacetyl-Leu-Asp-Val) derived from fibronectin. The search query was constructed using a model of 1 that was based upon the X-ray conformation of the related integrin-binding region of vascular cell adhesion molecule-1 (VCAM-1). The 3D search query consisted of the N-terminal cap and the carboxyl side chain of 1 because, upon the basis of existing structure-activity data on this series, these were known to be critical for high-affinity binding to alpha4beta1. The computational screen identified 12 reagents from a virtual library of 8624 molecules as satisfying the model and our synthetic filters. All of the synthesized compounds tested inhibit alpha4beta1 association with VCAM-1, with the most potent compound having an IC(50) of 1 nM, comparable to the starting compound. Using CATALYST, a 3D QSAR was generated that rationalizes the variation in activities of these alpha4beta1 antagonists. The most potent compound was evaluated in a sheep model of asthma, and a 30 mg nebulized dose was able to inhibit early and late airway responses in allergic sheep following antigen challenge and prevented the development of nonspecific airway hyperresponsiveness to carbachol. Our results demonstrate that it is possible to rapidly identify nonpeptidic replacements of integrin peptide antagonists. This approach should be useful in identification of nonpeptidic alpha4beta1 inhibitors with improved pharmacokinetic properties relative to their peptidic counterparts. 相似文献
1000.
Kim CY Whittington DA Chang JS Liao J May JA Christianson DW 《Journal of medicinal chemistry》2002,45(4):888-893
Carbonic anhydrase inhibitors are effective in lowering intraocular pressure, the primary indication of glaucoma. Human carbonic anhydrase II, and possibly carbonic anhydrase IV (CAII and CAIV, respectively), help regulate fluid secretion into the anterior chamber of the eye. Because inhibitors currently formulated as drugs to treat glaucoma were designed to target CAII, an understanding of the structural basis of CAII-CAIV discrimination by inhibitors would be useful for probing the role of each isozyme in the etiology of the disease. Here, we report the X-ray crystal structures of three novel thieno[3,2-e]-1,2-thiazine-6-sulfonamides complexed with CAII and the computationally predicted structures of the same compounds complexed with CAIV. All three compounds bind with similar affinity to CAII, but they bind with up to 100-fold lower affinities to CAIV. Comparisons of experimentally determined structures of CAII-inhibitor complexes and computationally predicted structures of CAIV-inhibitor complexes allow us to rationalize these affinity trends and outline molecular features that may contribute to high-affinity inhibitor binding to CAIV. This study demonstrates how experimental structure determination methods and computational structure prediction methods can be used together to answer questions that cannot be answered by either method alone. 相似文献