全文获取类型
收费全文 | 1689篇 |
免费 | 148篇 |
国内免费 | 6篇 |
专业分类
耳鼻咽喉 | 18篇 |
儿科学 | 43篇 |
妇产科学 | 6篇 |
基础医学 | 184篇 |
口腔科学 | 64篇 |
临床医学 | 170篇 |
内科学 | 250篇 |
皮肤病学 | 39篇 |
神经病学 | 114篇 |
特种医学 | 77篇 |
外科学 | 344篇 |
综合类 | 62篇 |
一般理论 | 1篇 |
预防医学 | 144篇 |
眼科学 | 22篇 |
药学 | 151篇 |
中国医学 | 5篇 |
肿瘤学 | 149篇 |
出版年
2021年 | 29篇 |
2020年 | 11篇 |
2019年 | 28篇 |
2018年 | 26篇 |
2017年 | 16篇 |
2016年 | 27篇 |
2015年 | 22篇 |
2014年 | 44篇 |
2013年 | 66篇 |
2012年 | 81篇 |
2011年 | 87篇 |
2010年 | 76篇 |
2009年 | 53篇 |
2008年 | 67篇 |
2007年 | 76篇 |
2006年 | 93篇 |
2005年 | 61篇 |
2004年 | 58篇 |
2003年 | 51篇 |
2002年 | 43篇 |
2001年 | 47篇 |
2000年 | 49篇 |
1999年 | 60篇 |
1998年 | 40篇 |
1997年 | 35篇 |
1996年 | 27篇 |
1995年 | 23篇 |
1994年 | 28篇 |
1993年 | 21篇 |
1992年 | 39篇 |
1991年 | 28篇 |
1990年 | 26篇 |
1989年 | 35篇 |
1988年 | 23篇 |
1987年 | 30篇 |
1986年 | 19篇 |
1985年 | 28篇 |
1984年 | 25篇 |
1983年 | 21篇 |
1982年 | 20篇 |
1980年 | 13篇 |
1979年 | 10篇 |
1977年 | 12篇 |
1976年 | 17篇 |
1974年 | 11篇 |
1971年 | 14篇 |
1970年 | 12篇 |
1969年 | 10篇 |
1968年 | 12篇 |
1967年 | 9篇 |
排序方式: 共有1843条查询结果,搜索用时 15 毫秒
11.
Subtotal thyroidectomy was performed for hyperthyroidism on 130 patients; 95 treated before surgery with propranolol (Group I) and 35 given only metoprolol before surgery (Group II). These patient groups were compared with reference to preoperative medication, operative and immediate postoperative course, and late results with follow-up for one to five years. Clinical response was 100% in group II and 94.7% in group I. The median length of preoperative treatment was 7.96 +/- 1.84 days in group I and 6.25 +/- 1.73 days in group II (P less than 0.05). There were no serious adverse effects of the drugs in either treatment group. No anaesthesiologic or cardiovascular complication occurred during operation in either group. Ten patients in group I (10.5%) and six patients in group II (11.4%) observed hyperthyroid manifestations in the immediate postoperative period, eliminated by the administration of the propranolol/metoprolol, and no case of thyroid storm occurred. One patient in group II developed clinical hypocalcaemia. Two patients, one in each group, presented temporary unilateral recurrent laryngeal nerve paralysis. There were two recurrences of toxicity in group I (2.1%) and none in group II. Hypothyroidism occurred in 3 patients (2.3%) two of them were from group I and one was from group II. The postoperative hospital stay was 4.62 +/- 1.61 days in group I and 2.81 +/- 1.32 days in group II (P less than 0.05). One patient from group I died on the third postoperative day due to pulmonary oedema. The results suggest that metoprolol can be safely used and offers the advantages of desired clinical response, shorter preoperative preparation time, simplicity of dosage and shorter postoperative hospital stay in comparison to propranolol for preoperative treatment of hyperthyroidism. 相似文献
12.
Interleukin 6: a fibroblast-derived growth inhibitor of human melanoma cells from early but not advanced stages of tumor progression.
下载免费PDF全文
![点击此处可从《Proceedings of the National Academy of Sciences of the United States of America》网站下载免费的PDF全文](/ch/ext_images/free.gif)
C Lu M F Vickers R S Kerbel 《Proceedings of the National Academy of Sciences of the United States of America》1992,89(19):9215-9219
Recently we reported that human dermal fibroblasts, or conditioned media obtained from such cells, affect the growth of human melanoma cells as a direct function of tumor progression: melanoma cells obtained from early-stage (metastatically incompetent) primary lesions were growth inhibited, whereas cells obtained from more advanced (metastatically competent) primary lesions, or metastases, were growth stimulated. Ion-exchange and gel-filtration chromatography of fibroblast conditioned medium revealed the inhibitor to be a protein of molecular mass between 20 and 30 kDa and distinct from the stimulator. This is the approximate molecular mass of interleukin 6 (IL-6), a ubiquitous multifunctional cytokine known to affect in particular many kinds of hemopoietic and lymphoid cells. Since this cytokine is known to be made by fibroblasts, we attempted to determine if the human fibroblast-derived growth inhibitor (hFDGI) was identical to IL-6. Neutralizing antibodies specific for IL-6 completely eliminated the inhibitory activity of hFDGI. Moreover, exposure to human recombinant IL-6 was found to inhibit the growth of early-stage melanoma cells obtained from radial growth phase (RGP) or early vertical growth phase (VGP) primary lesions in three of four cases. In contrast, melanoma cells from a number of more advanced VGP primary lesions, or from distant metastases, were completely resistant to this IL-6-mediated growth inhibition. Acquisition of an "IL-6-resistant" phenotype by metastatically competent melanoma cell variants may provide such cells with a proliferative advantage within the dermal mesenchyme (a hallmark of melanoma cells that are malignant), helping them eventually to dominate advanced primary lesions and to establish secondary growths elsewhere. 相似文献
13.
Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group 总被引:5,自引:0,他引:5
Haines JL; Terwedow HA; Burgess K; Pericak-Vance MA; Rimmler JB; Martin ER; Oksenberg JR; Lincoln R; Zhang DY; Banatao DR; Gatto N; Goodkin DE; Hauser SL 《Human molecular genetics》1998,7(8):1229-1234
Multiple sclerosis (MS) is a demyelinating autoimmune disease of the
central nervous system. While its etiology is not well understood, genetic
factors are clearly involved. Until recently, most genetic studies in MS
have been association studies using the case-control design testing
specific candidate genes and studying only sporadic cases. The only
consistently replicated finding has been an association with the HLA-DR2
allele within the major histocompatibility complex (MHC) on chromosome 6.
Using the genetic linkage design, however, evidence for and against linkage
of the MHC to MS has been found, fostering suggestions that sporadic and
familial MS have different etiologies. Most recently, two of four genomic
screens demonstrated linkage to the MHC, although specific allelic
associations were not tested. Here, a dataset of 98 multiplex families was
studied to test for an association to the HLA-DR2 allele in familial MS and
to determine if genetic linkage to the MHC was due solely to such an
association. Three highly polymorphic markers (HLA-DR, D6S273 and TNFbeta)
in the MHC demonstrated strong genetic linkage (parametric lod scores of
4.60, 2.20 and 1.24, respectively) and a specific association with the
HLA-DR2 allele was confirmed (TDT; P < 0.001). Stratifying the results
by HLA-DR2 status showed that the linkage results were limited to families
segregating HLA-DR2 alleles. These results demonstrate that genetic linkage
to the MHC can be explained by the HLA-DR2 allelic association. They also
indicate that sporadic and familial MS share a common genetic
susceptibility. In addition, preliminary calculations suggest that the MHC
explains between 17 and 62% of the genetic etiology of MS. This
heterogeneity is also supported by the minority of families showing no
linkage or association with loci within the MHC.
相似文献
14.
15.
Eltoum IA Eloubeidi MA Chhieng DC Tamhane A Crowe R Jhala D St John KD Wilcox CM Siegal GP Vickers S Jhala NC 《American journal of clinical pathology》2005,124(5):697-707
Our objectives were to devise a cytologic grading system and determine whether it would predict survival of patients with solid-type pancreatic adenocarcinoma. We evaluated 116 consecutive patients from July 2000 to November 2002; they were followed up until September 2003. We scored the following features on rapid Romanowsky-stained endoscopic ultrasound-guided fine-needle aspiration smears: cell group architecture, single cells, nuclear grade, mucus, bizarre cells, and necrosis. A cytologic grade (low vs high) was assigned. The Kaplan-Meier estimate of 6-month survival was 76% (SE, 7%) for patients with low-grade tumors vs 50% (SE, 6%) for patients with high-grade carcinoma. The median survival for patients with low-grade vs high-grade tumors was 1 year vs 6 months, respectively (chi2 = 4.45; P = .035). Cox proportional hazards regression showed tumor stage, cancer-specific treatment, and cytologic grade to be independent predictors of survival (P = .001). No other factors (age, mass location, placement of stent, presence of concomitant chronic pancreatitis, race, sex) predicted survival. We devised a grading system that independently predicted survival in patients with pancreatic adenocarcinoma. 相似文献
16.
Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation 总被引:22,自引:1,他引:22
Marsh DJ; Coulon V; Lunetta KL; Rocca-Serra P; Dahia PL; Zheng Z; Liaw D; Caron S; Duboue B; Lin AY; Richardson AL; Bonnetblanc JM; Bressieux JM; Cabarrot-Moreau A; Chompret A; Demange L; Eeles RA; Yahanda AM; Fearon ER; Fricker JP; Gorlin RJ; Hodgson SV; Huson S; Lacombe D; Eng C 《Human molecular genetics》1998,7(3):507-515
The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403
amino acid dual specificity phosphatase (protein tyrosine phosphatase;
PTPase), was shown recently to play a broad role in human malignancy.
Somatic PTEN deletions and mutations were observed in sporadic breast,
brain, prostate and kidney cancer cell lines and in several primary tumours
such as endometrial carcinomas, malignant melanoma and thyroid tumours. In
addition, PTEN was identified as the susceptibility gene for two hamartoma
syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or
Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD
families and seven BZS families was screened for germline PTEN mutations.
PTEN mutations were identified in 30 of 37 (81%) CD families, including
missense and nonsense point mutations, deletions, insertions, a
deletion/insertion and splice site mutations. These mutations were
scattered over the entire length of PTEN , with the exception of the first,
fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified
in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD
mutations identified in this exon. Seven of 30 (23%) were within the core
motif, the majority (five of seven) of which were missense mutations,
possibly pointing to the functional significance of this region. Germline
PTEN mutations were identified in four of seven (57%) BZS families studied.
Interestingly, none of these mutations was observed in the PTPase core
motif. It is also worthy of note that a single nonsense point mutation,
R233X, was observed in the germline DNA from two unrelated CD families and
one BZS family. Genotype-phenotype studies were not performed on this small
group of BZS families. However, genotype-phenotype analysis inthe group of
CD families revealed two possible associations worthy of follow-up in
independent analyses. The first was an association noted in the group of CD
families with breast disease. A correlation was observed between the
presence/absence of a PTEN mutation and the type of breast involvement
(unaffected versus benign versus malignant). Specifically and more
directly, an association was also observed between the presence of a PTEN
mutation and malignant breast disease. Secondly, there appeared to be an
interdependent association between mutations upstream and within the PTPase
core motif, the core motif containing the majority of missense mutations,
and the involvement of all major organ systems (central nervous system,
thyroid, breast, skin and gastrointestinal tract). However, these
observations would need to be confirmed by studying a larger number of CD
families.
相似文献
17.
Vickers SM Johnson LL Zou LQ Yannas IV Gibson LJ Spector M 《Tissue engineering》2004,10(7-8):1214-1223
Cells derived from synovium have drawn interest as donor cells for articular cartilage tissue engineering because they have been implicated in certain cartilage repair processes in vivo and the chondrogenic potential of the cells has been demonstrated in vitro. Studies have demonstrated that several other types of musculoskeletal connective tissue cells--including chondrocytes, fibrochondrocytes, ligament fibroblasts and osteoblasts, and mesenchymal stem cells can express the gene for the contractile actin isoform, alpha-smooth muscle actin (SMA), and can contract analogs of extracellular matrix in vitro. Although the physiological roles of SMA-enabled contraction of these cells have yet to be established, cell-mediated contraction of scaffolds employed for tissue engineering can alter the pore diameter of the matrix and distort its overall shape, and thus needs to be addressed. Toward this goal, the objective of this study was to investigate the expression of SMA by synovial cells and to evaluate their contraction of collagen-glycosaminoglycan (GAG) scaffolds. Synovial membranes obtained from the knees (stifle joints) of six adult dogs were evaluated for the presence of SMA by immunohistochemistry. Cells isolated from the synovial tissue were expanded through seven passages in monolayer culture, with samples from each passage allocated for Western blot analysis of SMA. Cells from passage 4 were seeded into porous type I collagen-GAG matrices and cultured for 4 weeks. Synovial cell-mediated contraction of the scaffolds was determined by measuring the diameters of the cell-seeded scaffolds and nonseeded controls every other day. Synovium-derived cells cultured as micropellets or in collagen-GAG matrices were incubated in chondrogenic medium with and without fetal bovine serum and evaluated for chondrogenesis by type II collagen immunohistochemistry. Immunohistochemistry revealed the presence of SMA in some cells (less than 10% of the cells) in the intimal layer of synovium from four of the five animals analyzed. Western blot analysis demonstrated a regular increase in the amount of SMA in the synovium-derived cells with passage number. Synovial cell-mediated contraction of the collagen-GAG scaffolds reached a value of 43% of the original diameter after 4 weeks, comparable to that found with other musculoskeletal cell types. Incubation of micropellet cultures of synovium-derived cells with chondrogenic medium revealed trace amounts of type II collagen production by immunohistochemistry. The findings of this study indicate that control of SMA-enabled contraction may be important when employing synovial cells for cartilage repair procedures, and warrant further investigation into the physiological role of SMA expression in synovial cells. 相似文献
18.
19.
20.
Unacceptable side effects involved in topical steroid usage for uveitis have prompted the search for alternative antiinflammatory drugs for the treatment of ocular inflammation. Cyclooxygenase inhibitors have been widely used for systemic inflammatory conditions over the last two decades and are therefore natural candidates to be studied for uveitis therapy. Previous studies of cyclooxygenase inhibitors in uveitis models yielded inconclusive and sometimes contradicting results. The authors compared the clinical effect of topical dexamethasone, diclofenac and placebo in an immunogenic uveitis model produced in ovalbumin immunized NZW rabbits challenged with ovalbumin in the vitreous. Nine clinical parameters of inflammation were compared employing a double blind placebo controlled protocol. Three groups of 16 eyes each, were assigned for each preparation and were followed for nine days with biomicroscopic examinations. Diclofenac was superior or equal to dexamethasone for iris hyperemia (p=0.059) and conjunctival injection (p=0.02), equal for corneal haziness and AC fibrin, yet inferior for corneal endothelial debris, iris fibrin and AC cells and flare (p<0.05). Placebo was inferior (p<0.05) to the other groups for the above mentioned parameters excluding fibrin precipitation on the iris that was greater in diclofenac treated eyes. While some clinical criteria of inflammation responded better to steroids than to diclofenac, the results of this study show that others responded better or equal to diclofenac. The authors hypothesize that although diclofenac reduces prostaglandin levels it may induce high levels of leukotrienes that maintain cellular exudation. 相似文献