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31.
Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism 总被引:3,自引:0,他引:3
Baron J; Winer KK; Yanovski JA; Cunningham AW; Laue L; Zimmerman D; Cutler GB Jr 《Human molecular genetics》1996,5(5):601-606
Parathyroid hormone secretion is negatively regulated by a 7- transmembrane
domain, G-protein coupled Ca(2+)-sensing receptor. We hypothesized that
activating mutations in this receptor might cause autosomal dominant
hypoparathyroidism (ADHP). Consistent with this hypothesis, we identified,
in two families with ADHP, heterozygous missense mutations in the
Ca(2+)-sensing receptor gene that cosegregated with the disorder. None of
50 normal controls had either mutation. We also identified a de novo,
missense Ca(2+)-sensing receptor mutation in a child with severe sporadic
hypoparathyroidism. The amino acid substitution in one ADHP family affected
the N-terminal, extracellular domain of the receptor. The other mutations
involved the transmembrane region. Unlike patients with acquired
hypoparathyroidism, patients with these mutations had hypercalciuria even
at low serum calcium concentrations. Their greater hypercalciuria
presumably reflected activation of Ca(2+)-sensing receptors in kidney
cells, where the receptor negatively regulates calcium reabsorption. This
augmented hypercalciuria increases the risk of renal complications and thus
has implications for the choice of therapy.
相似文献
32.
Targeting oncogenic interleukin‐7 receptor signalling with N‐acetylcysteine in T cell acute lymphoblastic leukaemia 下载免费PDF全文
Marc R. Mansour Casie Reed Amy R. Eisenberg Jen‐Chieh Tseng Jean‐Claude Twizere Sarah Daakour Akinori Yoda Scott J. Rodig Noa Tal Chen Shochat Alla Berezovskaya Daniel J. DeAngelo Stephen E. Sallan David M. Weinstock Shai Izraeli Andrew L. Kung Alex Kentsis A. Thomas Look 《British journal of haematology》2015,168(2):230-238
Activating mutations of the interleukin‐7 receptor (IL7R) occur in approximately 10% of patients with T cell acute lymphoblastic leukaemia (T‐ALL). Most mutations generate a cysteine at the transmembrane domain leading to receptor homodimerization through disulfide bond formation and ligand‐independent activation of STAT5. We hypothesized that the reducing agent N‐acetylcysteine (NAC), a well‐tolerated drug used widely in clinical practice to treat acetaminophen overdose, would reduce disulfide bond formation, and inhibit mutant IL7R‐mediated oncogenic signalling. We found that treatment with NAC disrupted IL7R homodimerization in IL7R‐mutant DND‐41 cells as assessed by non‐reducing Western blot, as well as in a luciferase complementation assay. NAC led to STAT5 dephosphorylation and cell apoptosis at clinically achievable concentrations in DND‐41 cells, and Ba/F3 cells transformed by an IL7R‐mutant construct containing a cysteine insertion. The apoptotic effects of NAC could be rescued in part by a constitutively active allele of STAT5. Despite using doses lower than those tolerated in humans, NAC treatment significantly inhibited the progression of human DND‐41 cells engrafted in immunodeficient mice. Thus, targeting leukaemogenic IL7R homodimerization with NAC offers a potentially effective and feasible therapeutic strategy that warrants testing in patients with T‐ALL. 相似文献
33.
Cystic nephromas are rare tumors of the kidney most commonly affecting boys or adult females. The fine-needle aspiration cytomorphology has not yet been described. A renal cystic mass in a 56 year old female was aspirated under ultrasound guidance. Papanicolaou stained smears of the cyst fluid revealed markedly atypical cells forming papillary clusters. Subsequent nephrectomy showed a typical cystic nephroma with lining epithelium resembling that seen in the aspirate. The cytomorphology of cystic nephroma has been misdiagnosed as renal cell carcinoma in the literature. Low cellularity, absence of necrosis, and paucity of single cells are features that should raise the possibility of cystic nephroma in a cystic renal mass. 相似文献
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Ying Mai Kung 《The Journal for Nurse Practitioners》2013,9(2):87-92
Influenza vaccination is recommended for all health care personnel (HCP), but immunization rates for this group continue to be suboptimal. This study explores relationships between individual characteristics, beliefs, knowledge, attitudes, and vaccination behavior through 2 surveys conducted at a university health center. The findings suggest that HCP who were vaccinated the year before, intended to be vaccinated next year, believed influenza vaccination was important, and were more knowledgeable are more likely to receive a vaccine. 相似文献
38.
Tai-Hsin Tsai Tzuu-Yuan Huang Sui-Sum Kung Yu-Feng Su Shiuh-Lin Hwang Ann-Shung Lieu 《The Kaohsiung journal of medical sciences》2013,29(10):540-546
Intraoperative intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were evaluated for use as prognostic indicators after surgery for severe traumatic brain injury (TBI), and threshold ICP and CPP values were determined to provide guidelines for patient management. This retrospective study reviewed data for 66 patients (20 females and 46 males) aged 13–83 years (average age, 48 years) who had received decompressive craniectomy and hematoma evacuation for severe TBI. The analysis of clinical characteristics included Glascow Coma Scale score, trauma mechanism, trauma severity, cerebral hemorrhage type, hematoma thickness observed on computed tomography scan, Glasgow Outcome Scale score, and mortality. Patients whose treatment included ICP monitoring had significantly better prognosis (p < 0.001) and significantly lower mortality (p = 0.016) compared to those who did not receive ICP monitoring. At all three major steps of the procedure, i.e., creation of the burr hole, evacuation of the hematoma, and closing of the wound, intraoperative ICP and CPP values significantly differed. The ICP and CPP values were also significantly associated with surgical outcome in the severe TBI patients. Between hematoma evacuation and wound closure, ICP and CPP values differed by 6.8 ± 4.5 and 6.5 ± 4.6 mmHg, respectively (mean difference, 6 mmHg). Intraoperative thresholds were 14 mmHg for ICP and 56mmH for CPP. Monitoring ICP and CPP during surgery improves management of severe TBI patients and provides an early prognostic indicator. During surgery for severe TBI, early detection of increased ICP is also crucial for enabling sufficiently early treatment to improve surgical outcome. However, further study is needed to determine the optimal intraoperative ICP and CPP thresholds before their use as subjective guidelines for managing severe TBI patients. 相似文献
39.
Zhenwei Su Xinliang Zhou Stephen H. Loukin W. John Haynes Yoshiro Saimi Ching Kung 《Pflügers Archiv : European journal of physiology》2009,458(5):861-867
Mechanosensitive (MS) ion channels likely underlie myriad force-sensing processes, from basic osmotic regulation to specified
sensations of animal hearing and touch. Albeit important, the molecular identities of many eukaryotic MS channels remain elusive,
let alone their working mechanisms. This is in stark contrast to our advanced knowledge on voltage- or ligand-sensitive channels.
Several members of transient receptor potential (TRP) ion channel family have been implicated to function in mechanosensation
and are recognized as promising candidate MS channels. The yeast TRP homolog, TRPY1, is clearly a first-line force transducer.
It can be activated by hypertonic shock in vivo and by membrane stretch force in excised patches under patch clamp, making
it a useful model for understanding TRP channel mechanosensitivity in general. TRPY1 offers two additional research advantages:
(1) It has a large (∼300 pS) unitary conductance and therefore a favorable S/N ratio. (2) Budding yeast allows convenient
and efficient genetic and molecular manipulations. In this review, we focus on the current research of TRPY1 and discuss its
prospect. We also describe the use of yeast as a system to express and characterize animal TRP channels. 相似文献
40.
B Martinac M Buechner A H Delcour J Adler C Kung 《Proceedings of the National Academy of Sciences of the United States of America》1987,84(8):2297-2301
We have used the patch-clamp electrical recording technique on giant spheroplasts of Escherichia coli and have discovered pressure-activated ion channels. The channels have the following properties: activation by slight positive or negative pressure; voltage dependence; large conductance; selectivity for anions over cations; dependence of activity on the species of permeant ions. We believe that these channels may be involved in bacterial osmoregulation and osmotaxis. 相似文献