全文获取类型
收费全文 | 901篇 |
免费 | 81篇 |
国内免费 | 22篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 50篇 |
妇产科学 | 14篇 |
基础医学 | 104篇 |
口腔科学 | 11篇 |
临床医学 | 94篇 |
内科学 | 171篇 |
皮肤病学 | 8篇 |
神经病学 | 52篇 |
特种医学 | 180篇 |
外科学 | 66篇 |
综合类 | 27篇 |
预防医学 | 57篇 |
眼科学 | 50篇 |
药学 | 70篇 |
中国医学 | 1篇 |
肿瘤学 | 47篇 |
出版年
2020年 | 7篇 |
2018年 | 6篇 |
2017年 | 9篇 |
2016年 | 8篇 |
2015年 | 12篇 |
2014年 | 24篇 |
2013年 | 28篇 |
2012年 | 16篇 |
2011年 | 19篇 |
2010年 | 23篇 |
2009年 | 18篇 |
2008年 | 18篇 |
2007年 | 33篇 |
2006年 | 23篇 |
2005年 | 28篇 |
2004年 | 24篇 |
2003年 | 17篇 |
2002年 | 9篇 |
2001年 | 16篇 |
2000年 | 17篇 |
1999年 | 25篇 |
1998年 | 40篇 |
1997年 | 39篇 |
1996年 | 41篇 |
1995年 | 25篇 |
1994年 | 22篇 |
1993年 | 35篇 |
1992年 | 24篇 |
1991年 | 16篇 |
1990年 | 31篇 |
1989年 | 35篇 |
1988年 | 36篇 |
1987年 | 28篇 |
1986年 | 22篇 |
1985年 | 32篇 |
1984年 | 13篇 |
1983年 | 18篇 |
1982年 | 25篇 |
1981年 | 13篇 |
1980年 | 11篇 |
1979年 | 9篇 |
1978年 | 7篇 |
1977年 | 13篇 |
1976年 | 22篇 |
1975年 | 9篇 |
1974年 | 5篇 |
1973年 | 5篇 |
1969年 | 4篇 |
1968年 | 8篇 |
1966年 | 9篇 |
排序方式: 共有1004条查询结果,搜索用时 15 毫秒
51.
Hyperuricemia and secondary urate nephropathy are uncommon in the paediatric setting outside of tumour lysis syndrome. We describe the case of a 12-year-old boy who presented at 3 years of age with acute renal failure. The cause of this remained unknown until the development of uric acid renal calculi 9 years later. This, and the availability of the previously unknown family history, provided the subsequent diagnosis of partial hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency. Detailed family history is important for early detection of this heterogeneous group of disorders. Early treatment may minimise long-term renal morbidity and mortality from renal insufficiency. 相似文献
52.
Tarsal navicular stress fractures: radiographic evaluation 总被引:3,自引:0,他引:3
Tarsal navicular stress fractures are a potential source of disabling foot pain in physically active individuals. The diagnosis of tarsal navicular stress fracture requires a high index of clinical and radiographic suspicion because the fracture is only rarely evident on routine radiographs or standard tomograms. The radiographic diagnosis of a tarsal navicular stress fracture may require anatomic anteroposterior tomograms or a radionuclide bone scan with plantar views. Radiographic examinations of 23 fractures in 21 patients are evaluated. 相似文献
53.
Antitumor activity of a kinesin inhibitor 总被引:7,自引:0,他引:7
Sakowicz R Finer JT Beraud C Crompton A Lewis E Fritsch A Lee Y Mak J Moody R Turincio R Chabala JC Gonzales P Roth S Weitman S Wood KW 《Cancer research》2004,64(9):3276-3280
Several members of the kinesin family of microtubule motor proteins play essential roles in mitotic spindle function and are potential targets for the discovery of novel antimitotic cancer therapies. KSP, also known as HsEg5, is a kinesin that plays an essential role in formation of a bipolar mitotic spindle and is required for cell cycle progression through mitosis. We identified a potent inhibitor of KSP, CK0106023, which causes mitotic arrest and growth inhibition in several human tumor cell lines. Here we show that CK0106023 is an allosteric inhibitor of KSP motor domain ATPase with a Ki of 12 nM. Among five kinesins tested, CK0106023 was specific for KSP. In tumor-bearing mice, CK0106023 exhibited antitumor activity comparable to or exceeding that of paclitaxel and caused the formation of monopolar mitotic figures identical to those produced in cultured cells. KSP was most abundant in proliferating human tissues and was absent from cultured postmitotic neurons. These findings are the first to demonstrate the feasibility of targeting mitotic kinesins for the treatment of cancer. 相似文献
54.
The Brk protein tyrosine kinase as a therapeutic target in cancer: opportunities and challenges 总被引:2,自引:0,他引:2
Brk is an intracellular protein tyrosine kinase that is significantly overexpressed in a majority of breast tumors, while being detected at appreciable levels in only a limited range of adult tissues that does not include the mammary gland. It has recently been demonstrated to have a role in promoting the proliferation of carcinoma cells, one that it is unlikely to perform in normal adult cells, and it therefore represents an exciting target for the development of novel cancer therapies based on specifically or selectively interfering with its functions. The strategy of pharmaceutical kinase inhibition is clinically proven and widely pursued in oncology programmes directed at a variety of tumor types. However, a potentially kinase-independent role for Brk in regulating proliferation suggests that alternative approaches, such as inhibiting protein-protein interactions, may prove more successful. Further research into Brk's signaling functions will underpin progress towards turning the potential suggested by these observations into rational drug discovery, from which a large number of patients stand to benefit. 相似文献
55.
A 26-year-old Asian woman presented with bilateral disk swelling, retinal exudates and infarcts. Evaluation found the underlying cause of the hypertensive optic neuropathy to be renal artery stenosis due to Takayasu's arteritis. 相似文献
56.
Diacylglycerol kinase alpha activity promotes survival of CD4+ 8+ double positive cells during thymocyte development 下载免费PDF全文
The diacylglycerol kinases (DGK) form a family of isoenzymes that catalyse the conversion of diacylglycerol (DAG) to phosphatidic acid (PA), both powerful second messengers in the cell. DGKalpha is expressed in brain, peripheral T cells and thymocytes and has been shown to translocate to the nuclear matrix upon T-cell receptor (TCR) engagement. Here, we show that high level expression of DGKalpha is induced following a signal transmitted through the pre-TCR and the protein tyrosine kinase, lck. Activity of DGKalpha contributes to survival in CD4+ 8+ (DP) thymocytes as pharmacological inhibition of DGK activity results in death of this cell population both in cell suspension and thymic explants. DGKalpha promotes survival in these thymocytes through a Bcl-regulated pathway. A consequence of inhibition of DGKalpha is the specific down-regulation of Bcl-xl, whereas in transgenic mice that over-express Bcl-2, death induced by the inhibitor is partially blocked. Thus we report a novel activity of DGKalpha in survival of thymocytes immediately after entry into the DP stage in development. 相似文献
57.
Hartung TK Allbutt H Dewar M Innes JA Crompton GK 《Respiration; international review of thoracic diseases》2002,69(4):314-319
BACKGROUND/OBJECTIVES: Environmentally friendly hydrofluoroalkane (HFA) pressurised metered-dose inhalers are currently being marketed to replace chlorofluorocarbon (CFC)-driven devices. It is uncertain whether these new formulations with different properties are acceptable to patients. Similarly, switching a patient to a dry powder inhaler (DPI) carries the risk of non-acceptance. METHODS: One hundred patients with obstructive airway disease on regular CFC aerosol inhaler medication underwent a standardised, structured interview. During the interview patients were asked to use a new HFA aerosol inhaler and three DPIs in random order. Patients' notions were recorded. RESULTS: Most patients (96) agreed to change from their CFC to the HFA inhaler, of those, only 12 did so with some reservation. Properties (taste, user-friendliness, design) of the HFA inhaler were rated favourably. DPIs represented an acceptable alternative to aerosol inhalers. In fact, 57 patients preferred a DPI over the HFA inhaler. Not all powder devices were equally acceptable. Replacing the CFC inhaler with patients' preferred alternative devices resulted in a more than 3-fold increase in costs. CONCLUSION: Concerns about the acceptability of reformulated CFC-free aerosol inhalers are ill founded. However, if given the choice, many patients prefer a DPI over the HFA inhaler. The transition offers an opportunity to review patients' current treatment and the proficiency of their inhaling technique. Moving to CFC-free inhalers will have revenue implications. 相似文献
58.
On the involvement of mitochondrial intermembrane junctional complexes in apoptosis 总被引:12,自引:0,他引:12
Crompton M 《Current medicinal chemistry》2003,10(16):1473-1484
The voltage dependent anion channel and the adenine nucleotide translocase are the principal proteins found in the mitochondrial outer and inner membranes, respectively. The two proteins can associate to form a junctional complex that establishes contact sites between the two membranes. This complex in turn recruits a range of proteins depending on the function to be executed. Among these, the junctional complexes can bind Bax and other proapoptotic proteins. Bax regulates the involvement of mitochondria in the apoptotic signalling pathway by controlling the the release of apoptogenic proteins from the mitochondrial intermembrane space to the cytosol. Another protein recruited to ANT is cyclophilin-D. Cyclophilin-D is a peptidylprolyl cis-trans-isomerase located in the intramitochondrial (matrix) compartment which stabilizes a "deformed" conformation of ANT in which its native gating properties are lost. Although the deformed state, when extensive, is lethal, cells can tolerate this conformational change when it occurs transiently. There is now a large body of data that implicates the voltage dependent anion channel, the adenine nucleotide translocase and cyclophilin-D, both separately and together, in the mitochondrial reactions of apoptosis. But there is no consensus over how, or indeed if, they are involved. This article examines the data relevant to this question and considers why a complex of these three proteins may be essential for the action of Bax and other proapoptotic proteins in permeabilizing the outer membrane to intermembrane space proteins. 相似文献
59.
Butler MW Mullan RH Schaffer KE Crotty TB Luke DA Donnelly SC 《Irish journal of medical science》2003,172(4):204-205
Background Hydatid disease is rare in Ireland and its incidence and prevalence are unknown. Most cases are diagnosed by a combination
of clinical findings, morphological features on imaging and by serological testing.
Aims We describe an Irish case of pulmonary hydatid disease detected at bronchoscopy by bronchoalveolar lavage, and discuss the
diagnosis and treatment of the disorder. 相似文献
60.
Shi YQ Li L Sanal O Tezcan I Emery GC Blattmann H Crompton NE 《International journal of radiation oncology, biology, physics》2001,49(2):555-559
PURPOSE: Cells from ataxia-telangiectasia (A-T) patients are extremely sensitive to radiation but display decreased apoptosis, as measured during the first 3 days following radiation. To explain this apparent contradiction, we examined apoptosis in normal and A-T cells at late time points following radiation, under the assumption that radiation-induced apoptosis is delayed in the A-T cells. METHODS AND MATERIALS: Blood cells and lymphoblastoid cell lines from A-T patients, as well as healthy donors, were irradiated with X-rays. Apoptosis was measured at different time points (up to 7 and 30 days for lymphocytes and lymphoblastoid cells, respectively) using a flow cytometric method based on the reduction of intracellular DNA content (sub-G1 population). RESULTS: Compared to normal cells, CD4 and CD8 A-T lymphocytes displayed constantly reduced levels of radiation-induced apoptosis for up to 7 days after treatment. A-T lymphoblastoid cells, however, displayed a delayed and prolonged apoptosis. CONCLUSION: A-T lymphoblastoid cells show high levels of delayed radiation-induced apoptosis, which may contribute to the high cellular radiosensitivity displayed by the A-T phenotype. ATM (the gene mutated in A-T) plays different roles in the apoptotic response to ionizing radiation in quiescent lymphocytes and proliferative lymphoblastoid cells. 相似文献