全文获取类型
收费全文 | 1037篇 |
免费 | 90篇 |
国内免费 | 8篇 |
专业分类
耳鼻咽喉 | 5篇 |
儿科学 | 147篇 |
妇产科学 | 10篇 |
基础医学 | 116篇 |
口腔科学 | 20篇 |
临床医学 | 114篇 |
内科学 | 151篇 |
皮肤病学 | 7篇 |
神经病学 | 12篇 |
特种医学 | 164篇 |
外科学 | 260篇 |
综合类 | 12篇 |
预防医学 | 37篇 |
眼科学 | 5篇 |
药学 | 37篇 |
中国医学 | 2篇 |
肿瘤学 | 36篇 |
出版年
2021年 | 5篇 |
2018年 | 10篇 |
2017年 | 5篇 |
2016年 | 10篇 |
2015年 | 20篇 |
2014年 | 18篇 |
2013年 | 23篇 |
2012年 | 23篇 |
2011年 | 32篇 |
2010年 | 28篇 |
2009年 | 27篇 |
2008年 | 26篇 |
2007年 | 27篇 |
2006年 | 29篇 |
2005年 | 33篇 |
2004年 | 26篇 |
2003年 | 26篇 |
2002年 | 32篇 |
2001年 | 21篇 |
2000年 | 26篇 |
1999年 | 28篇 |
1998年 | 53篇 |
1997年 | 68篇 |
1996年 | 46篇 |
1995年 | 37篇 |
1994年 | 39篇 |
1993年 | 26篇 |
1992年 | 28篇 |
1991年 | 21篇 |
1990年 | 16篇 |
1989年 | 31篇 |
1988年 | 30篇 |
1987年 | 33篇 |
1986年 | 32篇 |
1985年 | 25篇 |
1984年 | 16篇 |
1983年 | 8篇 |
1982年 | 17篇 |
1981年 | 13篇 |
1980年 | 18篇 |
1978年 | 10篇 |
1977年 | 16篇 |
1976年 | 8篇 |
1975年 | 10篇 |
1973年 | 5篇 |
1972年 | 6篇 |
1971年 | 8篇 |
1969年 | 6篇 |
1967年 | 4篇 |
1966年 | 6篇 |
排序方式: 共有1135条查询结果,搜索用时 15 毫秒
21.
22.
A 63-year-old man with iron loss anaemia and hypercalcaemia was found to have a renal cell carcinoma. Despite the iron-deficient blood and bone marrow picture, the serum ferritin concentration was markedly raised. This was mainly due to a “basic isoferritin”. The serum parathormone concentration was normal. The serum ferritin and calcium concentrations returned to normal after the tumour was removed. We propose that the renal cell carcinoma cells in this patient secreted the basic isoferritin as well as humoral factor(s) responsible for hypercalcaemia. 相似文献
23.
Gene conversion is a likely cause of mutation in PKD1 总被引:3,自引:0,他引:3
Watnick TJ; Gandolph MA; Weber H; Neumann HP; Germino GG 《Human molecular genetics》1998,7(8):1239-1243
Approximately 70% of the gene responsible for the most common form of
autosomal dominant polycystic kidney disease ( PKD1 ) is replicated in
several highly homologous copies located more proximally on chromosome 16.
We recently have described a novel technique for mutation detection in the
duplicated region of PKD1 that circumvents the difficulties posed by these
homologs. We have used this method to identify two patients with a nearly
identical cluster of base pair substitutions in exon 23. Since pseudogenes
are known to be reservoirs for mutation via gene conversion events for a
number of other diseases, we decided to test whether these sequence
differences in PKD1 could have arisen as a result of this mechanism. Using
changes in restriction digest patterns, we were able to show that these
sequence substitutions are also present in N23HA, a rodent-human somatic
cell hybrid that contains only the PKD1 homologs. Moreover, these changes
were also detected in total DNA from several affected and unaffected
individuals that did not harbor this mutation in their PKD1 gene copy. This
is the first example of gene conversion in PKD1 , and our findings
highlight the importance of using gene-specific reagents in defining PKD1
mutations.
相似文献
24.
Predominance of null mutations in ataxia-telangiectasia 总被引:15,自引:4,他引:15
Gilad S; Khosravi R; Shkedy D; Uziel T; Ziv Y; Savitsky K; Rotman G; Smith S; Chessa L; Jorgensen TJ; Harnik R; Frydman M; Sanal O; Portnoi S; Goldwicz Z; Jaspers NG; Gatti RA; Lenoir G; Lavin MF; Tatsumi K; Wegner RD; Shiloh Y; Bar-Shira A 《Human molecular genetics》1996,5(4):433-439
Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving
cerebellar degeneration, immunodeficiency, chromosomal instability,
radiosensitivity and cancer predisposition. The responsible gene, ATM, was
recently identified by positional cloning and found to encode a putative
350 kDa protein with a Pl 3-kinase-like domain, presumably involved in
mediating cell cycle arrest in response to radiation-induced DNA damage.
The nature and location of A-T mutations should provide insight into the
function of the ATM protein and the molecular basis of this pleiotropic
disease. Of 44 A-T mutations identified by us to date, 39 (89%) are
expected to inactivate the ATM protein by truncating it, by abolishing
correct initiation or termination of translation, or by deleting large
segments. Additional mutations are four smaller in-frame deletions and
insertions, and one substitution of a highly conserved amino acid at the Pl
3-kinase domain. The emerging profile of mutations causing A-T is thus
dominated by those expected to completely inactivate the ATM protein. ATM
mutations with milder effects may result in phenotypes related, but not
identical, to A-T.
相似文献
25.
Sanchez AA Johnston DA Myers C Edwards JE Mitchell AP Filler SG 《Infection and immunity》2004,72(1):598-601
Candida albicans must penetrate the endothelial cell lining of the vasculature to invade the deep tissues during a hematogenously disseminated infection. We compared 27 C. albicans mutants with their wild-type parent for their capacity to damage endothelial cells in vitro and cause a lethal infection in mice following tail vein inoculation. Of 10 mutants with significantly impaired capacity to damage endothelial cells, all had attenuated virulence. Therefore, the endothelial cell damage assay can be used as a screen to identify some virulence factors relevant to hematogenously disseminated candidiasis. 相似文献
26.
Prostaglandin F and E levels during endotoxin-induced pulmonary hypertension in calves 总被引:10,自引:0,他引:10
Anderson FL; Tsagaris TJ; Jubiz W; Kuida H 《The American journal of physiology》1975,228(5):1479-1482
27.
Reduced virulence of HWP1-deficient mutants of Candida albicans and their interactions with host cells 总被引:7,自引:0,他引:7
Tsuchimori N Sharkey LL Fonzi WA French SW Edwards JE Filler SG 《Infection and immunity》2000,68(4):1997-2002
The Candida albicans gene HWP1 encodes a surface protein that is required for normal hyphal development in vitro. We used mutants lacking one or both alleles of HWP1 to investigate the role of this gene in virulence. Mice infected intravenously with the homozygous hwp1 null mutant, CAL3, survived a median of >14 days, whereas mice infected with a control strain containing two functional alleles of HWP1 survived only 3.5 days. After 1 day of infection, all strains produced similar levels of infection in the kidneys, spleen, and blood. However, after 2 and 3 days, there was a significant decrease in the number of organisms in the kidneys of the mice infected with CAL3. This finding suggests that the hwp1 homozygous null mutant is normal in its ability to initiate infection but deficient in its capacity to maintain infection. CAL3 also germinated minimally in the kidneys. The ability of the heterozygous null mutant to germinate and cause mortality in mice was intermediate to CAL3, suggesting a gene dosage effect. To investigate potential mechanisms for the diminished virulence of CAL3, we examined its interactions with endothelial cells and neutrophils in vitro. CAL3 caused less endothelial cell injury than the heterozygous hwp1 mutant. We conclude that the HWP1 gene product is important for both in vivo hyphal development and pathogenicity of C. albicans. Also, the ability to form filaments may be critical for candidal virulence by enabling the fungus to induce cellular injury and maintain a deep-seated infection. 相似文献
28.
Candida albicans stimulates cytokine production and leukocyte adhesion molecule expression by endothelial cells. 总被引:4,自引:0,他引:4 下载免费PDF全文
S G Filler A S Pfunder B J Spellberg J P Spellberg J E Edwards Jr 《Infection and immunity》1996,64(7):2609-2617
Endothelial cells have the potential to influence significantly the host immune response to blood-borne microbial pathogens, such as Candida albicans. We investigated the ability (of this organism to stimulate endothelial cell responses relevant to host defense in vitro. Infection with C. albicans induced endothelial cells to express mRNAs encoding E-selectin, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, interleukin 6, interleukin 8, monocyte chemoattractant protein 1, and inducible cyclooxygenase (cox2). All three leukocyte adhesion molecule proteins were expressed on the surfaces of the endothelial cells after 8 h of exposure to C. albicans. An increase in secretion of all three cytokines was found after 12 h of infection. Cytochalasin D inhibited accumulation of the endothelial cell cytokine and leukocyte adhesion molecule mRNAs in response to C. albicans, suggesting that endothelial cell phagocytosis of the organism is required to induce this response. Live Candida tropicalis, Candida glabrata, a nongerminating strain of C. albicans, and killed C. albicans did not stimulate the expression of any of the cytokine or leukocyte adhesion molecule mRNAs. These findings indicate that a factor associated with live, germinating C. albicans is required for induction of endothelial cell mRNA expression. Furthermore, since endothelial cells phagocytize killed C. albicans, phagocytosis is likely necessary but not sufficient for this organism to stimulate mRNA accumulation. In conclusion, the secretion of proinflammatory cytokines and expression of leukocyte adhesion molecules by endothelial cells in response to C. albicans could enhance the host defense against this organism by contributing to the recruitment of activated leukocytes to sites of intravascular infection. 相似文献
29.
Sustained localized expression of ligand for the activating NKG2D receptor impairs natural cytotoxicity in vivo and reduces tumor immunosurveillance 总被引:11,自引:0,他引:11
Oppenheim DE Roberts SJ Clarke SL Filler R Lewis JM Tigelaar RE Girardi M Hayday AC 《Nature immunology》2005,6(9):928-937
Upregulation of the inducible gene products MICA (human) and Rae-1 (mouse) may promote tumor surveillance and autoimmunity by engaging the activating receptor NKG2D on natural killer (NK) cells and T cells. Nevertheless, sustained expression of MICA by tumors can also elicit NKG2D downregulation, perhaps indicating 'immunoevasion'. Investigating this paradox, we report here that constitutive Rae-1epsilon transgene expression in normal epithelium elicited local and systemic NKG2D downregulation, generalized but reversible defects in NK cell-mediated cytotoxicity and mild CD8(+) T cell defects. The extent of NKG2D downregulation correlated well with the incidence and progression of cutaneous carcinogenesis, emphasizing the utility of NKG2D as a marker of tumor resistance. Thus, NKG2D engagement is a natural mediator of immunosurveillance, which can be compromised by locally sustained ligand expression but potentially restored by innate immune activation. 相似文献
30.
OBJECTIVES: To review the traumatic injuries that have been associated with acupuncture and to discuss how these adverse effects may be reduced by increased awareness of normal anatomy and anatomical variations. METHODS: Literature search accompanied by postmortem anatomical studies. RESULTS: Traumatic lesions after acupuncture have been described in thoracic and abdominal viscera, in the peripheral and central nervous systems, and in blood vessels. Deaths have been recorded from pneumothorax and cardiac tamponade. The anatomical structure of the body at several acupuncture points is such that needles can reach vulnerable structures. CONCLUSION: While the frequency of adverse effects of acupuncture is unknown and they may be rare, knowledge of normal anatomy and anatomical variations is essential for safe practice and should be reviewed by regulatory bodies and those responsible for training courses. 相似文献