全文获取类型
收费全文 | 4054篇 |
免费 | 307篇 |
国内免费 | 5篇 |
专业分类
耳鼻咽喉 | 74篇 |
儿科学 | 132篇 |
妇产科学 | 74篇 |
基础医学 | 541篇 |
口腔科学 | 186篇 |
临床医学 | 529篇 |
内科学 | 528篇 |
皮肤病学 | 59篇 |
神经病学 | 299篇 |
特种医学 | 327篇 |
外科学 | 490篇 |
综合类 | 86篇 |
一般理论 | 3篇 |
预防医学 | 364篇 |
眼科学 | 87篇 |
药学 | 265篇 |
中国医学 | 2篇 |
肿瘤学 | 320篇 |
出版年
2022年 | 26篇 |
2021年 | 65篇 |
2020年 | 30篇 |
2019年 | 42篇 |
2018年 | 76篇 |
2017年 | 54篇 |
2016年 | 51篇 |
2015年 | 73篇 |
2014年 | 86篇 |
2013年 | 140篇 |
2012年 | 172篇 |
2011年 | 194篇 |
2010年 | 115篇 |
2009年 | 92篇 |
2008年 | 151篇 |
2007年 | 163篇 |
2006年 | 169篇 |
2005年 | 171篇 |
2004年 | 145篇 |
2003年 | 154篇 |
2002年 | 129篇 |
2001年 | 126篇 |
2000年 | 115篇 |
1999年 | 99篇 |
1998年 | 79篇 |
1997年 | 69篇 |
1996年 | 75篇 |
1995年 | 59篇 |
1994年 | 52篇 |
1993年 | 47篇 |
1992年 | 94篇 |
1991年 | 87篇 |
1990年 | 74篇 |
1989年 | 103篇 |
1988年 | 79篇 |
1987年 | 89篇 |
1986年 | 75篇 |
1985年 | 82篇 |
1984年 | 69篇 |
1983年 | 50篇 |
1982年 | 35篇 |
1981年 | 30篇 |
1980年 | 29篇 |
1979年 | 56篇 |
1978年 | 43篇 |
1977年 | 38篇 |
1976年 | 46篇 |
1975年 | 40篇 |
1973年 | 32篇 |
1972年 | 26篇 |
排序方式: 共有4366条查询结果,搜索用时 15 毫秒
41.
Adhesion of enteroaggregative Escherichia coli to pediatric intestinal mucosa in vitro. 总被引:2,自引:2,他引:2 下载免费PDF全文
Organ cultures of small- and large-intestinal mucosa from children were used to examine the interactions of enteroaggregative Escherichia coli (EAEC) with human intestine. Mucosae from patients aged between 3 and 190 months were cultured with five EAEC strains isolated from infants with diarrhea in the United Kingdom and with two well-described prototype EAEC strains, 17-2 and 221. The prototype strains adhered to jejunal, ileal, and colonic mucosae. The wild-type strains also adhered to this tissue but showed a variable pattern of adhesion: two adhered to all intestinal levels, one adhered to jejunum and ileum, one adhered to ileum only, and one adhered to ileum and colon. Adherence was in an aggregative or stacked-brick pattern, resembling that seen on HEp-2 cells. Electron microscopy of infected small intestinal mucosa revealed bacteria in association with a thick mucus layer above an intact enterocyte brush border, which contained extruded cell fragments. This mucus layer was not present on controls. EAEC adherence to colonic mucosa was associated with cytotoxic effects including microvillous vesiculation (but without evidence of an attaching/effacing lesion), enlarged crypt openings, the presence of intercrypt crevices, and increased epithelial cell extrusion. These results demonstrate that in vitro organ culture of intestinal mucosa from children can be used to investigate EAEC pathogenesis in childhood directly. EAEC strains appear able to colonize many regions of the gastrointestinal tract, without overt changes to small intestinal mucosa but with cytotoxic effects on colonic mucosa. 相似文献
42.
Telomere lengths of translocation-associated and nontranslocation-associated sarcomas differ dramatically 下载免费PDF全文
Montgomery E Argani P Hicks JL DeMarzo AM Meeker AK 《The American journal of pathology》2004,164(5):1523-1529
Sarcomas can be divided into those with specific translocations displaying monotonous cytomorphology, and those with complex karyotypes and marked cellular pleomorphism. Telomeres contain terminal DNA sequence repeats that maintain chromosomal stability. Telomeres shorten with cell division and may become dysfunctional leading to chromosomal instability. Using a fluorescence in situ hybridization/immunofluorescence method to assess telomere lengths in archival tissues we analyzed these two types of sarcomas using paraffin-embedded primary tumor specimens. Tissues from nine sarcomas with characteristic translocations (two synovial sarcomas, two alveolar rhabdomyosarcomas, two desmoplastic round cell tumors, and one each of infantile fibrosarcoma, myxoid liposarcoma, cellular congenital mesoblastic nephroma) and nine without (four malignant fibrous histiocytomas, two leiomyosarcomas, one pleomorphic rhabdomyosarcoma, one dedifferentiated chondrosarcoma, and one malignant peripheral nerve sheath tumor) were analyzed. In all (nine of nine) cases with specific translocations, which generally have few karyotypic abnormalities, telomere lengths were similar to or reduced compared to surrounding nonneoplastic tissues. In contrast, telomeres in cases lacking specific translocations, which generally contain complex karyotypes, were often found to be dramatically lengthened and heterogeneous. In addition to markedly elongated telomeres, seven of nine (78%) complex cases exhibited large brightly stained regions corresponding to a specific type of promyelocytic leukemia nuclear body found in immortalized cells that maintain telomeres in a telomerase-independent manner [alternative lengthening of telomeres (ALT) pathway]. This phenotype is unlike that of epithelial neoplasms that typically display complex karyotypes with abnormally short telomeres maintained by the enzyme telomerase. The discovery of heterogeneous telomere lengths and evidence of the ALT pathway in the majority of sarcomas with complex karyotypes supports the existence of a telomere maintenance pathway incapable of full karyotypic stabilization in pleomorphic sarcomas. These findings provide additional molecular-genetic evidence supporting the dichotomous grouping of sarcomas into those with characteristic signature translocations without extensive additional karyotypic abnormalities, and those without such signature translocations that typically display very complex karyotypes, and point to telomere dysfunction as a plausible contributor to the chromosomal aberrations found in complex sarcomas. 相似文献
43.
44.
The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis 总被引:5,自引:0,他引:5
Maheshwar MM; Cheadle JP; Jones AC; Myring J; Fryer AE; Harris PC; Sampson JR 《Human molecular genetics》1997,6(11):1991-1996
Tuberous sclerosis is an autosomal dominant trait in which the
dysregulation of cellular proliferation and differentiation results in the
development of hamartomatous growths in many organs. The TSC2 gene is one
of two genes determining tuberous sclerosis. Inactivating germline
mutations of TSC2 in patients with tuberous sclerosis and somatic loss of
heterozygosity at the TSC2 locus in the associated hamartomas indicate that
TSC2 functions as a tumour suppressor gene and that loss of function is
critical to expression of the tuberous sclerosis phenotype. The TSC2
product, tuberin, has a region of homology with the GTPase activating
protein rap1GAP and stimulates the GTPase activity of rap1a and rab5a in
vitro. Here we show that the region of homology between tuberin and human
rap1GAP and the murine GAP mSpa1 is more extensive than previously reported
and spans approximately 160 amino acid residues encoded within exons 34-38
of the TSC2 gene. Single strand conformation polymorphism analysis of these
exons in 173 unrelated patients with tuberous sclerosis and direct
sequencing of variant conformers together with study of additional family
members enabled characterisation of disease associated mutations in 14
cases. Missense mutations, which occurred in exons 36, 37 and 38 were
identified in eight cases, four of whom shared the same recurrent change
P1675L. Each of the five different missense mutations identified was shown
to occur de novo in at least one sporadic case of tuberous sclerosis. The
high proportion of missense mutations detected in the region of the TSC2
gene encoding the GAP-related domain supports its key role in the
regulation of cellular growth.
相似文献
45.
Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis 总被引:7,自引:2,他引:7
Li DY; Toland AE; Boak BB; Atkinson DL; Ensing GJ; Morris CA; Keating MT 《Human molecular genetics》1997,6(7):1021-1028
Supravalvular aortic stenosis (SVAS) is an inherited obstructive vascular
disease that affects the aorta, carotid, coronary and pulmonary arteries.
Previous molecular genetic data have led to the hypothesis that SVAS
results from mutations in the elastin gene, ELN. In these studies, the
disease phenotype was linked to gross DNA rearrangements (35 and 85 kb
deletions and a translocation) in three SVAS families. However, gross
rearrangements of ELN have not been identified in most cases of autosomal
dominant SVAS. To define the spectrum of ELN mutations responsible for this
disorder, we refined the genomic structure of human ELN and used this
information in mutational analyses. ELN point mutations co-segregate with
the disease in four familial cases and are associated with SVAS in three
sporadic cases. Two of the mutations are nonsense, one is a single base
pair deletion and four are splice site mutations. In one sporadic case, the
mutation arose de novo. These data demonstrate that point mutations of ELN
cause autosomal dominant SVAS.
相似文献
46.
47.
48.
R. S. Pickard P. L. Joseph A. J. Collins R. C. J. Hicks 《Medical & biological engineering & computing》1979,17(2):261-267
Photofabrication techniques have been used to produce a nickel-iron microelectrode array on Kapton film specifically designed
for biological implantation. The probe is 2·5 mm×2 mm and carries four tissue terminals, each 2 μm in width. Both spontaneous
and evoked potentials have been recorded from frog sciatic nerve. Developmental possibilities for the probe are fully discussed. 相似文献
49.
T M Grogan M J Hicks C S Jolley C S Rangel S E Jones 《Laboratory investigation; a journal of technical methods and pathology》1984,51(5):504-514
To resolve the controversy over the immunologic nature of nodular mixed lymphoma (NM), we examined nine cases of NM for surface antigens using both tissue section and cell suspension methods. These were contrasted with 12 cases of nodular poorly differentiated lymphocytic lymphoma. We found two major B cell types of NM, those with monoclonal immunoglobulin (SIg+)-positive nodules with an SIg+B1+B2+Ia+T- phenotype (four cases) and those with nodules devoid of immunoglobulin with an SIg-B1+B2-Ia+T- phenotype (five cases). Our SIg+ NM cases appear similar to nodular poorly differentiated lymphocytic lymphoma (SIg+B1+B2+Ia+T-), except suspension assay indicates fewer SIg+ cells in NM. In our SIg- NM cases, the neoplastic nodules consistently expressed B1 and Ia-like antigens and lacked T cells, indicating a B cell neoplasm similar to many large cell lymphomas. By demonstrating a B cell antigen in SIg- nodules, we substantially resolve the controversial NM cases previously called "null" or T cell. The two distinct immunotypes indicate the complexity of B cell antigenic expression in NM and might also explain the variable response to therapy in NM described in previous studies. Finally, we describe NM cases with the simultaneous occurrence of several stages of B cell differentiation. This suggests that some NM cases are not frozen in a single stage of B cell development but may express a range of B cell antigens. NM, then, may be a paradigm of variable, simultaneous B cell maturation. 相似文献
50.
Lipoblastoma is a relatively rare tumor that occurs in infancy and early childhood and arises from embryonic white fat. Although a benign tumor, lipoblastomas tend to recur and may resemble myxoid liposarcoma. The authors report 26 cases over a 15-year period at Texas Children's Hospital. There was a slight female predilection (14F:12M). The most common symptom was a painless mass with or without increasing size. The trunk, extremities, head and neck, retroperitoneum, inguinal canal, peritoneal cavity, and lung were the tumor sites. Most tumors were circumscribed lipoblastomas and the minority were diffuse infiltrative lipoblastomatosis. Reexcision for residual or recurrent tumor was necessary more frequently in patients with lipoblastomatosis. Histopathologic examination and ultrastructural examination revealed cellular neoplasms composed of immature adipocytes with relatively well-defined septa, frequent lipoblasts, a fine vascular network, and often a myxoid appearance resembling myxoid liposarcoma. Cytogenetics was performed in 4 cases with chromosome 8q abnormality being most common. The major concern with lipoblastoma in children is to completely excise the tumor to avoid leaving residual tumor and to prevent recurrences. Confusion with myxoid liposarcoma, well-differentiated liposarcoma, and typical lipomas may occur. Although asymptomatic, lipoblastomas may cause dysfunction of other organ systems due to mass effect. Complete surgical excision with at least 2 years of follow-up is the preferred therapy. 相似文献