全文获取类型
收费全文 | 116462篇 |
免费 | 9014篇 |
国内免费 | 392篇 |
专业分类
耳鼻咽喉 | 1258篇 |
儿科学 | 3064篇 |
妇产科学 | 2069篇 |
基础医学 | 16676篇 |
口腔科学 | 2575篇 |
临床医学 | 11840篇 |
内科学 | 24569篇 |
皮肤病学 | 2350篇 |
神经病学 | 12320篇 |
特种医学 | 4808篇 |
外国民族医学 | 6篇 |
外科学 | 16189篇 |
综合类 | 1416篇 |
一般理论 | 80篇 |
预防医学 | 9179篇 |
眼科学 | 1916篇 |
药学 | 7852篇 |
中国医学 | 132篇 |
肿瘤学 | 7569篇 |
出版年
2023年 | 569篇 |
2022年 | 1166篇 |
2021年 | 2348篇 |
2020年 | 1466篇 |
2019年 | 2205篇 |
2018年 | 2698篇 |
2017年 | 2029篇 |
2016年 | 2404篇 |
2015年 | 2764篇 |
2014年 | 3617篇 |
2013年 | 4838篇 |
2012年 | 7398篇 |
2011年 | 7548篇 |
2010年 | 4376篇 |
2009年 | 4022篇 |
2008年 | 6603篇 |
2007年 | 7036篇 |
2006年 | 6596篇 |
2005年 | 6496篇 |
2004年 | 6091篇 |
2003年 | 5450篇 |
2002年 | 5352篇 |
2001年 | 2356篇 |
2000年 | 2258篇 |
1999年 | 2140篇 |
1998年 | 1409篇 |
1997年 | 1158篇 |
1996年 | 945篇 |
1995年 | 957篇 |
1994年 | 851篇 |
1993年 | 760篇 |
1992年 | 1457篇 |
1991年 | 1391篇 |
1990年 | 1283篇 |
1989年 | 1266篇 |
1988年 | 1138篇 |
1987年 | 1028篇 |
1986年 | 1029篇 |
1985年 | 1011篇 |
1984年 | 837篇 |
1983年 | 720篇 |
1982年 | 633篇 |
1981年 | 548篇 |
1980年 | 461篇 |
1979年 | 626篇 |
1978年 | 500篇 |
1977年 | 463篇 |
1975年 | 427篇 |
1974年 | 472篇 |
1973年 | 426篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Eukaryotic cells invest a large proportion of their genome in maintaining telomere length homeostasis. Among the 173 non-essential yeast genes found to affect telomere length, a large proportion is involved in vacuolar traffic. When mutated, these vacuolar protein-sorting (VPS) genes lead to telomeres shorter than those observed in the wild type. Using genetic analysis, we characterized the pathway by which VPS15, VPS34, VPS22, VPS23 and VPS28 affect the telomeres. Our results indicate that these VPS genes affect telomere length through a single pathway and that this effect requires the activity of telomerase and the Ku heterodimer, but not the activity of Tel1p or Rif2p. We present models to explain the link between vacuolar traffic and telomere length homeostasis. 相似文献
992.
Perceptual speed does not cause intelligence, and intelligence does not cause perceptual speed 总被引:2,自引:0,他引:2
Luciano M Posthuma D Wright MJ de Geus EJ Smith GA Geffen GM Boomsma DI Martin NG 《Biological psychology》2005,70(1):1-8
There is ongoing debate whether the efficiency of local cognitive processes leads to global cognitive ability or whether global ability feeds the efficiency of basic processes. A prominent example is the well-replicated association between inspection time (IT), a measure of perceptual discrimination speed, and intelligence (IQ), where it is not known whether increased speed is a cause or consequence of high IQ. We investigated the direction of causation between IT and IQ in 2012 genetically related subjects from Australia and The Netherlands. Models in which the reliable variance of each observed variable was specified as a latent trait showed IT correlations of -0.44 and -0.33 with respective Performance and Verbal IQ; heritabilities were 57% (IT), 83% (PIQ) and 77% (VIQ). Directional causation models provided poor fits to the data, with covariation best explained by pleiotropic genes (influencing variation in both IT and IQ). This finding of a common genetic factor provides a better target for identifying genes involved in cognition than genes which are unique to specific traits. 相似文献
993.
Rajpar MH Koch MJ Davies RM Mellody KT Kielty CM Dixon MJ 《Human molecular genetics》2002,11(21):2559-2565
Dentine dysplasia type II is an autosomal dominant disorder in which mineralization of the dentine of the primary teeth is abnormal. On the basis of the phenotypic overlap between, and shared chromosomal location with, dentinogenesis imperfecta type II, a second disorder of dentine mineralization, it has been proposed that the two conditions are allelic. As recent studies have shown that dentinogenesis imperfecta type II results from mutation of the bicistronic dentine sialophosphoprotein gene (DSPP ), we have tested this hypothesis by sequencing DSPP in a family with a history of dentine dysplasia type II. Our results have shown that a missense change, which causes the substitution of a tyrosine for an aspartic acid in the hydrophobic signal peptide domain of the protein, underlies the phenotype in this family. Biochemical analysis has further demonstrated that this mutation causes a failure of translocation of the encoded proteins into the endoplasmic reticulum, and is therefore likely to lead to a loss of function of both dentine sialoprotein and dentine phosphoprotein. 相似文献
994.
Obesity and the risk of heart failure 总被引:1,自引:0,他引:1
Kenchaiah S Evans JC Levy D Wilson PW Benjamin EJ Larson MG Kannel WB Vasan RS 《The New England journal of medicine》2002,347(5):305-313
995.
A. A. Cruz F. Lima E. Sarinho G. Ayre C. Martin H. Fox P. J. Cooper 《Clinical and experimental allergy》2007,37(2):197-207
BACKGROUND: Although the role of immunoglobulin E (IgE) in immunity against helminth parasites is unclear, there is concern that therapeutic antibodies that neutralize IgE (anti-IgE) may be unsafe in subjects at risk of helminth infection. OBJECTIVE: We conducted an exploratory study to investigate the safety of omalizumab (anti-IgE) in subjects with allergic asthma and/or perennial allergic rhinitis at high risk of intestinal helminth infection. The primary safety outcome was risk of infections with intestinal helminths during anti-IgE therapy. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in 137 subjects (12-30 years) at high risk of geohelminth infection. All subjects received pre-study anthelmintic treatment, followed by 52 weeks' treatment with omalizumab or placebo. RESULTS: Of the omalizumab subjects 50% (34/68) experienced at least one intestinal geohelminth infection compared with 41% (28/69) of placebo subjects [odds ratio (OR) 1.47, 95% confidence interval (CI) 0.74-2.95, one-sided P=0.14; OR (adjusted for study visit, baseline infection status, gender and age) 2.2 (0.94-5.15); one-sided P=0.035], providing some evidence for a potential increased incidence of geohelminth infection in subjects receiving omalizumab. Omalizumab therapy was well tolerated, and did not appear to be associated with increased morbidity attributable to intestinal helminths as assessed by clinical and laboratory adverse events, maximal helminth infection intensities and additional anthelmintic requirements. Time to first infection (OR 1.30, 95% CI 0.79-2.15, one-sided P=0.15) was similar between treatment groups. Infection severity and response to anthelmintics appeared to be unaffected by omalizumab therapy. CONCLUSIONS: In this exploratory study of allergic subjects at high risk of helminth infections, omalizumab therapy appeared to be safe and well tolerated, but may be associated with a modest increase in the incidence of geohelminth infection. 相似文献
996.
Characterization of melanocyte stimulating hormone receptor variant alleles in twins with red hair 总被引:7,自引:3,他引:7
The association between MSHR coding region variation and hair colour in
humans has been examined by genotyping 25 red haired and 62 non-red
Caucasians, all of whom were 12 years of age and members of a twin pair
study. Twelve amino acid substitutions were seen at 11 different sites,
nine of these being newly described MSHR variants. The previously reported
Val92Met allele shows no association with hair colour, but the three
alleles Arg151Cys, Arg160Trp and Asp294His were associated with red hair
and one Val60Leu variant was most frequent in fair/blonde and light brown
hair colours. Variant MSHR genotypes are associated with lighter skin types
and red hair (P < 0.001). However, comparison of the MSHR genotypes in
dizygotic twin pairs discordant for red hair colour indicates that the MSHR
gene cannot be solely responsible for the red hair phenotype, since five of
13 pairs tested had both haplotypes identical by state (with three of the
five having both identical by descent). Rather, it is likely that
additional modifier genes exist, making variance in the MSHR gene necessary
but not always sufficient, for red hair production.
相似文献
997.
Nguyen K Bassez G Bernard R Krahn M Labelle V Figarella-Branger D Pouget J Hammouda el H Béroud C Urtizberea A Eymard B Leturcq F Lévy N 《Human mutation》2005,26(2):165
DYSF encoding dysferlin is mutated in Miyoshi myopathy and Limb-Girdle Muscular Dystrophy type 2B, the two main phenotypes recognized in dysferlinopathies. Dysferlin deficiency in muscle is the most relevant feature for the diagnosis of dysferlinopathy and prompts the search for mutations in DYSF. DYSF, located on chromosome 2p13, contains 55 coding exons and spans 150 kb of genomic DNA. We performed a genomic analysis of the DYSF coding sequence in 34 unrelated patients from various ethnic origins. All patients showed an absence or drastic decrease of dysferlin expression in muscle. A primary screening of DYSF using SSCP or dHPLC of PCR products of each of 55 exons of the gene was followed by sequencing whenever a sequence variation was detected. All together, 54 sequence variations were identified in DYSF, 50 of which predicting either a truncated protein or one amino-acid substitution and most of them (34 out of 54) being novel. In 23 patients, we identified two pathogenic mutations, while only one was identified in 11 patients. These mutations were widely spread in the coding sequence of the gene without any mutational "hotspot." 相似文献
998.
999.
A developing therapy for complete or partial loss of function in various tissues and organs involves transplanting an appropriate cell population, capable of compensating for the existing deficiencies. Clinical application of this type of strategy is currently limited by the death or dedifferentiation of the transplanted cells after delivery to the recipient. A delay in thorough vascularization of the implant area creates an environment low in oxygen and other nutrients, and likely contributes to the initial death of transplanted cells. We have addressed this problem by sustained delivery of vascular endothelial growth factor (VEGF), an initiator of angiogenesis, from a porous polymer matrix utilized simultaneously for cell delivery. As expected from previous studies, VEGF delivered from these constructs elicited an enhanced angiogenic response over a 2-week period when implanted subcutaneously in SCID mice. Hepatocytes implanted using VEGF-containing matrices demonstrated significantly greater survival after 1 week in vivo as compared with cells implanted on matrices without growth factor. The results of this study therefore indicate that enhancing vascularization in the location of transplanted cells promotes their survival. In addition, this delivery system may be used in future studies to directly promote cell survival and function by also providing growth factors specific to the transplanted cells. 相似文献
1000.
Immunomagnetic enrichment and detection of isolated tumor cells in bone marrow of patients with epithelial malignancies 总被引:5,自引:0,他引:5
Weihrauch MR Skibowski E Draube A Geller A Tesch H Diehl V Bohlen H 《Clinical & experimental metastasis》2002,19(7):617-621
The detection of isolated tumor cells (ITC) in the bone marrow of patients with epithelial malignancies is an independant
prognostic factor for several entities as breast cancer, colorectal cancer or non-small lung cancer. However, with conventional
immunocytology using Ficoll density gradient and APAAP staining, only a small proportion of the bone marrow samples can be
scanned for cytokeratin-positive (CK+) cells. To improve detection rates, we evaluated the enrichment of ITC by magnetic activated
cell sorting (MACS) compared to regularly stained cytospins. Recovery experiments with a CK+ breast cancer cell line (SKBR3)
were performed to calculate the MACS enrichment rate. Bone marrow was obtained by aspiration from 20 patients with carcinomas
of epithelial origin and from 17 controls. ITC were enriched and stained with magnetically labeled CAM 5.2 antibodies directed
to cytokeratin 7 and 8. MACS of SKBR3 seeded in peripheral blood revealed average recovery rates of 62% and 48% and average
enrichment factors of 104-fold and 8139-fold of the CK+ cells after one and after two separations, respectively. After immunomagnetic
enrichment, CK+ cells were detected in 16 of 20 (80%) cancer patients, whereas only 7 (35%) patients showed CK+ cells without
magnetic enrichment (P=0.002). Ten of twelve (83%) patients with metastatic disease (stage M1) and six of eight (75%) patients without any overt metastases (M0) had CK+ cells in their bone marrow. None of the negative controls showed any CK+ cells. Enrichment with magnetically labeled
anti cytokeratin antibodies increases the detection rate of epithelial cells in bone marrow of cancer patients compared to
immunocytology.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献