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81.
82.
Won-Gyu Choi Masatsugu Toyota Su-Hwa Kim Richard Hilleary Simon Gilroy 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(17):6497-6502
Their sessile lifestyle means that plants have to be exquisitely sensitive to their environment, integrating many signals to appropriate developmental and physiological responses. Stimuli ranging from wounding and pathogen attack to the distribution of water and nutrients in the soil are frequently presented in a localized manner but responses are often elicited throughout the plant. Such systemic signaling is thought to operate through the redistribution of a host of chemical regulators including peptides, RNAs, ions, metabolites, and hormones. However, there are hints of a much more rapid communication network that has been proposed to involve signals ranging from action and system potentials to reactive oxygen species. We now show that plants also possess a rapid stress signaling system based on Ca2+ waves that propagate through the plant at rates of up to ∼400 µm/s. In the case of local salt stress to the Arabidopsis thaliana root, Ca2+ wave propagation is channeled through the cortex and endodermal cell layers and this movement is dependent on the vacuolar ion channel TPC1. We also provide evidence that the Ca2+ wave/TPC1 system likely elicits systemic molecular responses in target organs and may contribute to whole-plant stress tolerance. These results suggest that, although plants do not have a nervous system, they do possess a sensory network that uses ion fluxes moving through defined cell types to rapidly transmit information between distant sites within the organism.Plants are constantly tailoring their responses to current environmental conditions via a complex array of chemical regulators that integrate developmental and physiological programs across the plant body. Environmental stimuli are often highly localized in nature, but the subsequent plant response is often elicited throughout the entire organism. For example, soil is a highly heterogeneous environment and the root encounters stimuli that are presented in a patchy manner. Thus, factors including dry or waterlogged regions of the soil, variations in the osmotic environment, and stresses such as elevated levels of salt are all likely to be encountered locally by individual root tips, but the information may have to be acted on by the plant as a whole.In animals, long-range signaling to integrate activities across the organism occurs through rapid ionic/membrane potential-driven signaling through the nervous system in addition to operating via long-distance chemical signaling. Plants have also been proposed to possess a rapid, systemic communication network, potentially mediated through signals ranging from changes in membrane potential/ion fluxes (1–3) and levels of reactive oxygen species (ROS) (4, 5) to altered hydraulics in the vasculature (6). Even so, the molecular mechanisms behind rapid, systemic signaling in plants and whether such signals indeed carry regulatory information remains largely unknown. Suggestions that Ca2+ channels play a role in signals that occlude sieve tube elements (7), or that mediate systemic electrical signaling (2) in response to remote wounding, highlight Ca2+-dependent signaling events as a strong candidate for mediating some of these long-range responses. Similarly, cooling of roots elicits Ca2+ increases in the shoot within minutes (8), suggesting systemic signals can elicit Ca2+-dependent responses at distal sites within the plant. However, despite extensive characterization of Ca2+ signals (reviewed in ref. 9), their roles in a possible plant-wide communication network remain poorly understood. Therefore, to visualize how Ca2+ might act in local and systemic signaling, we generated Arabidopsis plants expressing the highly sensitive, GFP-based, cytoplasmic Ca2+ sensor YCNano-65 (10). We observed that a range of abiotic stresses including H2O2, touch, NaCl, and cold shock triggered Ca2+ increases at the point of application. However, NaCl also elicited a Ca2+ increase that moved away from the point of stress application. Propagation of this Ca2+ increase was associated with subsequent systemic changes in gene expression. We also report that this salt stress-induced long-distance Ca2+ wave is dependent on the activity of the ion channel protein Two Pore Channel 1 (TPC1), which also appears to contribute to whole-plant stress tolerance. 相似文献
83.
Bisoprolol fumarate (bisoprolol) is a β-blocker widely used to treat chronic heart failure (CHF). However, few studies have compared its efficacy and safety with those of the widely used β-blocker carvedilol in Japanese patients with CHF. We designed a confirmatory trial of bisoprolol using carvedilol as a control drug; however, the trial was discontinued after an off-label use of bisoprolol was approved during the study. Bisoprolol and carvedilol were administered for 32 weeks in 31 and 28 patients, respectively. The mean maintenance doses of bisoprolol and carvedilol were 3.3 and 13.6 mg/day, respectively, and the mean durations of treatment were 188.2 and 172.9 days, respectively. Heart-rate changes were similar in both groups. The mean changes from baseline to Week 32 in left ventricular (LV) ejection fraction (EF) (bisoprolol vs carvedilol groups; 11.7 % ± 8.6 % vs 10.1 % ± 10.5 %), LV end-diastolic volume (?37.5 ± 48.7 vs ?24.7 ± 29.4 ml), and LV end-systolic volume (?41.9 ± 43.0 vs ?29.3 ± 25.9 ml) revealed a decrease in LV volume and an increase in LVEF in both groups. The cumulative event-free rate for a composite of cardiovascular death or admissions to hospital for worsening of CHF was 92.4 % and 94.7 % in the bisoprolol and carvedilol groups, respectively. Overall, 90.3 % and 85.7 % of patients were titrated up to the maintenance doses of bisoprolol and carvedilol, respectively. Bisoprolol, at half the dose used in other countries, is well tolerated and is as effective as carvedilol for treating Japanese patients with mild to moderate CHF. 相似文献
84.
Shinichi Kako Yoshinobu Kanda Makoto Onizuka Nobuyuki Aotsuka Kensuke Usuki Takayoshi Tachibana Takeshi Kobayashi Jun Kato Shingo Yano Hiroaki Shimizu Katsuhiro Shono Masatsugu Tanaka Shokichi Tsukamoto Takehiko Mori Etsuko Yamazaki Yuho Najima Akira Hangaishi Takumi Hoshino Reiko Watanabe Kenji Matsumoto Shinichiro Okamoto for Kanto Study Group for Cell Therapy 《American journal of hematology》2020,95(3):251-257
The optimal pre-transplant conditioning for aplastic anemia (AA) remains unclear. We performed a prospective study on allogeneic transplantation from a related or unrelated donor for adult patients with AA. We assessed whether reduced-dose cyclophosphamide (CY) could decrease toxicity while maintaining engraftment, and low-dose thymoglobulin could safely prevent graft-vs-host disease (GVHD). The pre-transplant conditioning regimen consisted of fludarabine 120 mg/m2, CY 100 mg/kg, and thymoglobulin 2.5 mg/kg with or without 2 Gy of total body irradiation. Twenty-seven patients with a median age of 36 years were analyzed. Sixteen patients received graft from related donors. The stem cell source was bone marrow in 26 patients. All of the patients but one, who died early, achieved neutrophil engraftment at a median of 19 days. Mixed chimerism was observed in six and five patients at days 30 and 90, respectively. Only one patient experienced secondary engraftment failure with complete donor-type chimerism. None of the patients developed severe acute GVHD. The cumulative incidence of chronic GVHD was 37.7% at 1 year. The overall survival rate was 96.3% at 1 year and 3 years. A high EB virus-DNA load was detected in one patient at days 60. No one developed EBV-lymphoproliferative disorder within a year. The results suggest that the conditioning regimen in this study was safe and effective. However, relatively high incidence of chronic GVHD needs further improvement. 相似文献
85.
Yoshibumi Antoku Masao Takemoto Takahiro Mito Akihiro Masumoto Masatsugu Nozoe Atsushi Tanaka Yusuke Yamamoto Takafumi Ueno Takuya Tsuchihashi 《Internal medicine (Tokyo, Japan)》2020,59(22):2831
Objective We recently reported that routine cardiac computed tomography (CT) scans for radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) could steadily detect coronary artery lesions (CALs) and could accurately detect myocardial ischemia in 9% of patients with AF who underwent RFCA of AF. The aim of this study was to identify the independent risk factor (s) of myocardial ischemia in those patients. Methods Patient characteristics, blood test, CALs, Ordinal coronary calcium scoring (OCCS), and myocardial Ischemia (MI) were evaluated in 757 consecutive patients who underwent RFCA of AF. Results There were 685 and 72 patients without and with myocardial ischemia, respectively. A univariate analysis and multivariate statistical analysis revealed that a male gender (Odds ratio 2.11), a high number of co-existing coronary risk factors (NCCRF ≥3) (Odds ratio 2.03), an elevated brain natriuretic peptide level (BNP ≥100 pg/mL) (Odds ratio 3.37), an enlarged left atrial volume (≥90 mL) (Odds ratio 2.91), and a high OCCS (≥4) (Odds ratio 13.0) were independent risk factors of myocardial ischemia in patients undergoing RFCA of AF. Conclusion The high OCCS (≥4) by cardiac CT was the strongest independent risk factor of myocardial ischemia in those patients. However, physicians may be able to find the high risk patients of myocardial ischemia by evaluating a male gender, in the presence of a high NCCRF (≥3) and elevated BNP (≥100 pg/mL) without OCCS by cardiac CT in patients undergoing RFCA of AF. 相似文献
86.
Ayyappan Anitha Ismail Thanseem Kazuhiko Nakamura Mahesh M. Vasu Kazuo Yamada Takatoshi Ueki Yoshimi Iwayama Tomoko Toyota Kenji J. Tsuchiya Yasuhide Iwata Katsuaki Suzuki Toshiro Sugiyama Masatsugu Tsujii Takeo Yoshikawa Norio Mori 《Journal of psychiatry & neuroscience : JPN》2014,39(5):294-303
Background
In a genome-wide association study of autism, zinc finger protein 804A (ZNF804A) single nucleotide polymorphisms (SNPs) were found to be nominally associated in verbally deficient individuals with autism. Zinc finger protein 804A copy number variations (CNVs) have also been observed in individuals with autism. In addition, ZNF804A is known to be involved in theory of mind (ToM) tasks, and ToM deficits are deemed responsible for the communication and social challenges faced by individuals with autism. We hypothesized that ZNF804A could be a risk gene for autism.Methods
We examined the genetic association and CNVs of ZNF804A in 841 families in which 1 or more members had autism. We compared the expression of ZNF804A in the postmortem brains of individuals with autism (n = 8) and controls (n = 13). We also assessed in vitro the effect of ZNF804A silencing on the expression of several genes known to be involved in verbal efficiency and social cognition.Results
We found that rs7603001 was nominally associated with autism (p = 0.018). The association was stronger (p = 0.008) in the families of individuals with autism who were verbally deficient (n = 761 families). We observed ZNF804A CNVs in 7 verbally deficient boys with autism. In ZNF804A knockdown cells, the expression of synaptosomal-associated protein, 25kDa (SNAP25) was reduced compared with controls (p = 0.009). The expression of ZNF804A (p = 0.009) and SNAP25 (p = 0.009) were reduced in the anterior cingulate gyrus (ACG) of individuals with autism. There was a strong positive correlation between the expression of ZNF804A and SNAP25 in the ACG (p < 0.001).Limitations
Study limitations include our small sample size of postmortem brains.Conclusion
Our results suggest that ZNF804A could be a potential candidate gene mediating the intermediate phenotypes associated with verbal traits in individuals with autism. 相似文献87.
88.
Hiromichi Ishiyama Takefumi Satoh Masashi Kitano Ken-ichi Tabata Shouko Komori Masaomi Ikeda Itaru Soda Shinji Kurosaka Akane Sekiguchi Masaki Kimura Shogo Kawakami Masatsugu Iwamura Kazushige Hayakawa 《Journal of radiation research》2014,55(3):509-517
The purpose of this study was to report the outcomes of high-dose-rate (HDR) brachytherapy and hypofractionated external beam radiotherapy (EBRT) combined with long-term androgen deprivation therapy (ADT) for National Comprehensive Cancer Network (NCCN) criteria-defined high-risk (HR) and very high-risk (VHR) prostate cancer. Data from 178 HR (n = 96, 54%) and VHR (n = 82, 46%) prostate cancer patients who underwent 192Ir-HDR brachytherapy and hypofractionated EBRT with long-term ADT between 2003 and 2008 were retrospectively analyzed. The mean dose to 90% of the planning target volume was 6.3 Gy/fraction of HDR brachytherapy. After five fractions of HDR treatment, EBRT with 10 fractions of 3 Gy was administered. All patients initially underwent ≥6 months of neoadjuvant ADT, and adjuvant ADT was continued for 36 months after EBRT. The median follow-up was 61 months (range, 25–94 months) from the start of radiotherapy. The 5-year biochemical non-evidence of disease, freedom from clinical failure and overall survival rates were 90.6% (HR, 97.8%; VHR, 81.9%), 95.2% (HR, 97.7%; VHR, 92.1%), and 96.9% (HR, 100%; VHR, 93.3%), respectively. The highest Radiation Therapy Oncology Group-defined late genitourinary toxicities were Grade 2 in 7.3% of patients and Grade 3 in 9.6%. The highest late gastrointestinal toxicities were Grade 2 in 2.8% of patients and Grade 3 in 0%. Although the 5-year outcome of this tri-modality approach seems favorable, further follow-up is necessary to validate clinical and survival advantages of this intensive approach compared with the standard EBRT approach. 相似文献
89.
90.
Takeshi Azuma Masamichi Hirai Shigeji Ito Kenji Yamamoto R. Thomas Taggart Takao Matsuba Kiyoshi Yasukawa Kouji Uno Takanobu Hayakumo Masatsugu Nakajima 《International journal of cancer. Journal international du cancer》1996,67(4):492-497
Ductal cancers of the pancreas frequently express markers of gastrointestinal epithelial cells. Cathepsin E (CTSE) is a non-secretory, intracellular, but non-lysosomal proteinase found in the highest concentration in the superficial epithelial cells of the stomach. The aims of our study were to examine the expression of CTSE in the pancreas, to establish an assay system of CTSE and to evaluate the diagnostic usefulness of CTSE in the pancreatic juice. Eleven patients with pancreatic ductal adenocarcinoma, 10 with mucin-producing adenoma, 3 with intraductal papillary hyperplasia and 43 with chronic pancreatitis were examined. Surgically resected pancreatic tissues were subjected to immunohistochemistry for CTSE. Pancreatic juice was collected from the patients and subjected to sandwich ELISA and Western analysis for detecting CTSE. Positive staining for CTSE was observed in pancreatic ductal adenocarcinoma by immunohistochemistry. CTSE was also expressed in mucin-producing adenoma, intraductal papillary hyperplasia and mucinous hyperplasia. CTSE in the pancreatic juice was present in 8 of 11 patients with pancreatic ductal adenocarcinoma, 5 of 10 patients with mucin-producing tumor, 1 of 3 patients with intraductal papillary hyperplasia and 4 of 43 patients with chronic pancreatitis. The detection frequency of CTSE in the pancreatic juice was significantly higher in the patients with pancreatic ductal adenocarcinoma than in the patients with chronic pancreatitis. Our findings suggest that the expression of CTSE is associated with the pathogenesis of pancreatic ductal adenocarcinoma, that CTSE in the pancreatic juice seems to be a useful marker for a definitive diagnosis and that CTSE may be expressed at a relatively early stage of multistep carcinogenesis in pancreatic lesions. © 1996 Wiley-Liss, Inc. 相似文献