全文获取类型
收费全文 | 980篇 |
免费 | 71篇 |
国内免费 | 18篇 |
专业分类
耳鼻咽喉 | 10篇 |
儿科学 | 50篇 |
妇产科学 | 19篇 |
基础医学 | 120篇 |
口腔科学 | 46篇 |
临床医学 | 122篇 |
内科学 | 202篇 |
皮肤病学 | 36篇 |
神经病学 | 44篇 |
特种医学 | 134篇 |
外科学 | 105篇 |
综合类 | 47篇 |
预防医学 | 51篇 |
眼科学 | 5篇 |
药学 | 47篇 |
中国医学 | 2篇 |
肿瘤学 | 29篇 |
出版年
2023年 | 6篇 |
2022年 | 4篇 |
2021年 | 13篇 |
2020年 | 13篇 |
2019年 | 23篇 |
2018年 | 22篇 |
2017年 | 20篇 |
2016年 | 21篇 |
2015年 | 26篇 |
2014年 | 35篇 |
2013年 | 41篇 |
2012年 | 34篇 |
2011年 | 15篇 |
2010年 | 56篇 |
2009年 | 47篇 |
2008年 | 30篇 |
2007年 | 42篇 |
2006年 | 21篇 |
2005年 | 30篇 |
2004年 | 19篇 |
2003年 | 16篇 |
2002年 | 19篇 |
2001年 | 10篇 |
2000年 | 16篇 |
1999年 | 18篇 |
1998年 | 47篇 |
1997年 | 40篇 |
1996年 | 37篇 |
1995年 | 26篇 |
1994年 | 34篇 |
1993年 | 29篇 |
1992年 | 8篇 |
1991年 | 9篇 |
1990年 | 10篇 |
1989年 | 21篇 |
1988年 | 20篇 |
1987年 | 22篇 |
1986年 | 13篇 |
1985年 | 11篇 |
1984年 | 11篇 |
1983年 | 13篇 |
1982年 | 16篇 |
1981年 | 12篇 |
1980年 | 15篇 |
1978年 | 6篇 |
1977年 | 13篇 |
1976年 | 12篇 |
1975年 | 5篇 |
1974年 | 6篇 |
1972年 | 4篇 |
排序方式: 共有1069条查询结果,搜索用时 0 毫秒
31.
Identification of the multiple endocrine neoplasia type 1 (MEN1) gene. The European Consortium on MEN1 总被引:10,自引:0,他引:10
Lemmens I; Van de Ven WJ; Kas K; Zhang CX; Giraud S; Wautot V; Buisson N; De Witte K; Salandre J; Lenoir G; Pugeat M; Calender A; Parente F; Quincey D; Gaudray P; De Wit MJ; Lips CJ; Hoppener JW; Khodaei S; Grant AL; Weber G; Kytola S; Teh BT; Farnebo F; Thakker RV 《Human molecular genetics》1997,6(7):1177-1183
32.
Morphological analysis of degeneration and regeneration of syncytiotrophoblast in first trimester placental villi during organ culture 总被引:3,自引:1,他引:3
We have recently shown using dansyl-L-lysine exclusion studies that the
release of human chorionic gonadotrophin (HCG) in conjunction with L-
lactate dehydrogenase (LDH) from first trimester villi during organ culture
is symptomatic of syncytiotrophoblast degeneration. The purpose of this
study was to examine chorionic villi at the ultrastructural level in order
to determine events occurring during organ culture. The tissue was sampled
after 0, 24, 48 and 120 h in culture and processed for electron microscopy.
In addition to confirming the previously recorded syncytial degeneration,
the electron micrographs showed clearly the generation of a new
syncytiotrophoblast layer. The new layer, derived from differentiating
cytotrophoblast cells, was largely formed by 48 h and was maintained for at
least 120 h in culture. This study demonstrates a model which provides an
opportunity to study the differentiation of cytotrophoblast cells whilst
they retain their anatomical relationships within the villous structure.
相似文献
33.
34.
Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1) 总被引:10,自引:1,他引:10
Rousseau F; el Ghouzzi V; Delezoide AL; Legeai-Mallet L; Le Merrer M; Munnich A; Bonaventure J 《Human molecular genetics》1996,5(4):509-512
Thanatophoric dwarfism (TD) is a sporadic lethal skeletal dysplasia with
micromelic shortening of the limbs, macrocephaly, platyspondyly and reduced
thoracic cavity. In the most common subtype (TD1), femurs are curved, while
in TD2, straight femurs are associated with cloverleaf skull. Mutations in
the fibroblast growth factor receptor 3 (FGFR3) gene were identified in
both subtypes. While TD2 was accounted for by a single recurrent mutation
in the tyrosine kinase 2 domain, TD1 resulted from either stop codon
mutations or missense mutations in the extracellular domain of the gene.
Here, we report the identification of FGFR3 mutations in 25/26 TD cases.
Two novel missense mutations (Y373C and G370C) were detected in 8/26 and
1/26 TD1 cases respectively. Both mutations created cysteine residues in
the juxta extramembrane domain of the receptor. Sixteen cases carried the
previously reported R248C (9/26 cases), S249C (2/26 cases) or stop codon
FGFR3 mutations (5/26 cases). Our results suggest that TD1 is a genetically
homogeneous condition and give additional support to the view that newly
created cysteine residues in the extracellular domain of the protein play a
key role in the severity of the disease.
相似文献
35.
KJ Champion C Bunag AL Estep JR Jones CH Bolt RC Rogers KA Rauen DB Everman 《Clinical genetics》2011,79(5):468-474
Champion KJ, Bunag C, Estep AL, Jones JR, Bolt CH, Rogers RC, Rauen KA, Everman DB. Germline mutation in BRAF codon 600 is compatible with human development: de novo p.V600G mutation identified in a patient with CFC syndrome. BRAF, the protein product of BRAF, is a serine/threonine protein kinase and one of the direct downstream effectors of Ras. Somatic mutations in BRAF occur in numerous human cancers, whereas germline BRAF mutations cause cardio‐facio‐cutaneous (CFC) syndrome. One recurrent somatic mutation, p.V600E, is frequently found in several tumor types, such as melanoma, papillary thyroid carcinoma, colon cancer, and ovarian cancer. However, a germline mutation affecting codon 600 has never been described. Here, we present a patient with CFC syndrome and a de novo germline mutation involving codon 600 of BRAF, thus providing the first evidence that a pathogenic germline mutation involving this critical codon is not only compatible with development but can also cause the CFC phenotype. In vitro functional analysis shows that this mutation, which replaces a valine with a glycine at codon 600 (p.V600G), leads to increased ERK and ELK phosphorylation compared to wild‐type BRAF but is less strongly activating than the cancer‐associated p.V600E mutation. 相似文献
36.
H4 acetylation, XIST RNA and replication timing are coincident and define x;autosome boundaries in two abnormal X chromosomes 总被引:2,自引:1,他引:2
The inactive X (Xi) differs from its active homologue (Xa) in a number of
ways, including increased methylation of CpG islands, replication late in S
phase, underacetylation of histone H4 and association with XIST RNA. Global
changes in DNA methylation occur relatively late in development, but the
other properties all change during or shortly after the establishment of Xi
and may play a role in the mechanism by which an inactive chromatin
conformation spreads across most of the chromosome. In the present report,
we use two human X;autosome translocation chromosomes to study the
spreading of inactive X chromatin across X;autosome boundaries. In one of
these chromosomes, t(X;6), Xp distal to p11.2 is replaced by 6p21.1-6pter
and, in the other, ins(X;16), a small fragment derived from 16p13 is
inserted into the distal third of Xq. In lymphoid cells from patients
carrying these translocations in an unbalanced form, Xi was shown by HUMARA
assay to be derived exclusively [t(X:6)] or predominantly [ins (X;16)] from
the derived X chromosome. We used a combination of immunolabelling and
RNA/DNA fluorescence in situ hybridization to define the distribution of
XIST RNA, deacetylated H4 and late-replicating DNA across the two derived X
chromosomes in inactive form. Within the limits of the cytogenetic
techniques employed, the results show complete coincidence of these three
parameters, with all three being excluded from the autosomal component of
the derived X chromosome.
相似文献
37.
Janneke AL van Kempen Henk J Schers Anne Jacobs Sytse U Zuidema Franca Ruikes Sarah HM Robben René JF Melis Marcel GM Olde Rikkert 《The British journal of general practice》2013,63(608):e225-e231
Background
Primary care is increasingly interested in the identification of frailty, as it selects the target population for integrated care. However, instruments for the identification of frailty specifically validated for use in primary care are scarce. This study developed the Easycare Two-step Older persons Screening (Easycare-TOS), which provides a valid, efficient, and pragmatic screening procedure to identify frail older people.Aim
This paper aims to describe the development of the Easycare-TOS and the data from the pilot studies.Design and setting
Observational pilot study in seven academic GP practices in and around Nijmegen, The Netherlands.Method
The Easycare-TOS was developed in a cyclic process with the input of stakeholders. In every cycle, the requirements were first defined, then translated into a prototype that was tested in a pilot study. The Easycare-TOS makes optimal use of prior knowledge of the GP, and the professionals’ appraisal is decisive in the frailty decision, instead of a cut-off score. Further, it considers aspects of frailty, as well as aspects of the care context of the patient.Results
The pilot data have shown that after step 1, two-thirds of the patients do not need further assessment, because they are judged as not frail, based on prior knowledge of the GP. The overall prevalence of frailty in this pilot study is 24%. Most professionals who participated in the pilot studies considered the time investment acceptable and the method to be of added value.Conclusion
The Easycare-TOS instrument meets the predefined efficiency, flexibility, and acceptability requirements for use as an identification instrument for frailty in primary care. 相似文献38.
NA Hanchard DR Murdock PL Magoulas M Bainbridge D Muzny YQ Wu M Wang AL McGuire JR Lupski RA Gibbs CW Brown 《Clinical genetics》2013,83(5):457-461
The advent of whole‐exome next‐generation sequencing (WES) has been pivotal for the molecular characterization of Mendelian disease; however, the clinical applicability of WES has remained relatively unexplored. We describe our exploration of WES as a diagnostic tool in a 3½‐year old female patient with a 2‐year history of episodic muscle weakness and paroxysmal dystonia who presented following a previous extensive but unrevealing diagnostic work‐up. WES was performed on the proband and her two parents. Parental exome data was used to filter potential de novo genomic events in the proband and suspected variants were confirmed using di‐deoxy sequencing. WES revealed a de novo non‐synonymous mutation in exon 21 of the calcium channel gene CACNA1S that has been previously reported in a single patient as a rare cause of atypical hypokalemic periodic paralysis. This was unexpected, as the proband's original differential diagnosis had included hypokalemic periodic paralysis, but clinical and laboratory features were equivocal, and standard clinical molecular testing for hypokalemic periodic paralysis and related disorders was negative. This report highlights the potential diagnostic utility of WES in clinical practice, with implications for the approach to similar diagnostic dilemmas in the future. 相似文献
39.
Christopher B. Harte Ph.D. Gabrielle I. Liverant Ph.D. Denise M. Sloan Ph.D. Barbara W. Kamholz Ph.D. Laina E. Rosebrock B.A. Maurizio Fava M.D. Gary B. Kaplan M.D. 《Annals of behavioral medicine》2013,46(1):73-80
Background
Both depression and smoking have been independently associated with lower heart rate variability (HRV), suggesting dysregulation of cardiac autonomic function. However, no studies have systematically explored the effects of smoking on HRV among depressed patients.Purpose
This study examined differences in HRV based on smoking status among depressed individuals.Methods
Electrophysiological data were examined among 77 adult outpatients without a history of myocardial infarction, who met criteria for major depressive disorder or dysthymia. Frequency domain [low frequency (LF), high frequency (HF), LF/HF ratio, respiratory sinus arrhythmia (RSA)] parameters of HRV, and heart rate and inter-beat interval (IBI) data were compared between depressed smokers (n?=?34) and depressed nonsmokers (n?=?44).Results
After controlling for covariates, depressed smokers, compared to depressed nonsmokers, displayed significantly lower LF, HF, and RSA.Conclusions
Among depressed patients, smoking is associated with significantly lower HRV, indicating dysregulated autonomic modulation of the heart. 相似文献40.
Oyen RH; Gielen JL; Van Poppel HP; Verbeken EK; Van Damme BJ; Baert LV; Baert AL 《Radiology》1988,169(3):705-707
Abdominal radiography, excretory urography, retrograde pyelography, and computed tomography were performed in two patients who had undergone retrograde pyelography with thorium dioxide (Thorotrast) approximately 40 years ago. Both patients developed a transitional cell carcinoma due to suburothelial thorium deposition. Typical thorium densities were demonstrated at CT in the peripelvicalyceal area as well as in retroperitoneal lymph nodes. Elderly patients in whom radiographic examination reveals retained Thorotrast in the kidney should be followed up because of the high risk of renal carcinoma. 相似文献